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W1988595972 abstract "Expression analysis of a novel cDNA isolated from immortal murine fibroblasts revealed a single transcript of 3.0 kilobase pairs that was highly expressed in mouse and human striated muscle and in mouse heart. The gene has therefore been named striamin. Its expression was confined to skeletal muscle types with a fast glycolytic (2B) contractile phenotype. It was also detected in C2C12 mouse myoblasts and was down-regulated during in vitro myogenesis. The cDNA has a single open reading frame encoding a predicted 16.8-kDa protein of 149 amino acids with no homology to known proteins. Microinjection and transfection of green fluorescence protein-taggedstriamin demonstrated that it localizes to the nucleus. Coimmunoprecipitations revealed that it can interact with p53 (a positive marker for myoblast differentiation) in vivo andin vitro. Furthermore, it repressed p53 activity in p53-mediated reporter assays. Fluorescence in situhybridization with a mouse P1 genomic clone localized the gene to chromosome 12C3, which is syntenic to human chromosome 14q21–22. Expression analysis of a novel cDNA isolated from immortal murine fibroblasts revealed a single transcript of 3.0 kilobase pairs that was highly expressed in mouse and human striated muscle and in mouse heart. The gene has therefore been named striamin. Its expression was confined to skeletal muscle types with a fast glycolytic (2B) contractile phenotype. It was also detected in C2C12 mouse myoblasts and was down-regulated during in vitro myogenesis. The cDNA has a single open reading frame encoding a predicted 16.8-kDa protein of 149 amino acids with no homology to known proteins. Microinjection and transfection of green fluorescence protein-taggedstriamin demonstrated that it localizes to the nucleus. Coimmunoprecipitations revealed that it can interact with p53 (a positive marker for myoblast differentiation) in vivo andin vitro. Furthermore, it repressed p53 activity in p53-mediated reporter assays. Fluorescence in situhybridization with a mouse P1 genomic clone localized the gene to chromosome 12C3, which is syntenic to human chromosome 14q21–22. Several genes, such as muscle creatine kinase, troponins, caveolin-3, α-actin, and myosin, have been reported to be predominantly expressed in skeletal muscle. A family of muscle-specific transcription factors such as myoD, myogenin, myf-5, and MRF-4/herculin/myf-6 that regulate muscle-specific gene expression has also been cloned. These are phosphorylated nuclear proteins, containing helix-loop-helix motifs required for dimerization and DNA binding, that can determine a specific cellular differentiation program (1Olson E.N. Klein W.H. Genes Dev. 1994; 8: 1-8Crossref PubMed Scopus (606) Google Scholar). The myoD family of transcription factors has been shown to direct myogenesis, repress proliferation, activate differentiation, and induce contractile phenotypes. The introduction of any one of these into nonmyogenic cells induces their differentiation into mature muscle cells (2Weintraub H. Davis R. Tapscott S. Thayer M. Krause M. Benezra R. Blackwell T.K. Turner D. Rupp R. Hollenberg S. Zhuang Y. Lassar A.B. Science. 1991; 251: 761-766Crossref PubMed Scopus (1226) Google Scholar). The MyoD and myf-5 are expressed in proliferating myoblasts whereas myogenin and MRF-4 are not expressed until myoblasts exit the cell cycle in response to mitogen depletion. Therefore, myoD and myf-5 have been im- plicated as having a role in proliferating myoblasts whereas myogenin and MRF-4 have been shown to activate and maintain muscle gene expression (3Emerson C.P.J. Curr. Opin. Cell Biol. 1993; 5: 1057-1064Crossref PubMed Scopus (34) Google Scholar). In addition, the cell cycle regulatory proteins such as RB (4Shiio Y. Sawada J.I. Handa H. Yamamoto T. Inoue J.I. Oncogene. 1996; 12: 1837-1845PubMed Google Scholar, 5Wang J. Guo K. Wills K.N. Walsh K. Cancer Res. 1997; 57: 351-354PubMed Google Scholar), p21 (6Guo K. Wang J. Andres V. Smith R.C. Walsh K. Mol. Cell. Biol. 1995; 15: 3823-3829Crossref PubMed Scopus (361) Google Scholar), cyclin D, cdk2, cdk4 (7Kiess M. Gill R.M. Hamel P.A. Oncogene. 1995; 10: 159-166PubMed Google Scholar), and p53 (8Soddu S. Blandino G. Scardigli R. Coen S. Marchetti A. Rizzo M.G. Bossi G. Cimino L. Crescenzi M. Sacchi A. J. Cell Biol. 1996; 134: 193-204Crossref PubMed Scopus (121) Google Scholar) have been implicated in the muscle differentiation program. Recently, caveolin-3, α-dystroglycan, and DNA methyltransferase (9Song K.S. Scherer P.E Tang Z. Okamoto T. Li S. Chafel M. Chu D. Kohtz D.S. Lisanti M.P. J. Cell Biol. 1996; 271: 15160-15165Scopus (606) Google Scholar, 10Kostrominova T.Y. Tanzer M.L. J. Cell. Biochem. 1995; 58: 527-534Crossref PubMed Scopus (21) Google Scholar, 11Takagi H. Tajima S. Asano A. Eur. J. Biochem. 1995; 231: 282-291Crossref PubMed Scopus (47) Google Scholar) have also been assigned a positive role in myogenic differentiation.While looking for genes involved in senescence and immortalization, we fortuitously cloned a novel gene that is specifically expressed in fast twitch skeletal muscles. The gene is named “striamin” because of its specific expression in striated muscle. Cloning of the cDNA, expression analyses, subcellular localization, chromosomal assignment, its interactions with the tumor suppressor p53, and its possible significance during muscle differentiation are reported herein.DISCUSSIONHere we report cloning and characterization of a novel gene,striamin, whose expression is restricted to the striated muscles. The expression pattern of striamin shares features in common with a few other genes, but is most similar to that of MyoD. Both are expressed in proliferating myoblasts, decline during differentiation, and yet are present in adult skeletal muscle (26Hughes S.M. Taylor J.M. Tapscott S.J. Gurley C.M. Carter W.J. Peterson C.A. Development. 1993; 118: 1137-1147Crossref PubMed Google Scholar). Furthermore, they appear to be preferentially expressed in fast glycolytic muscle fibers in the adult mouse (27Hughes S.M. Koishi K. Rudnicki M. Maggs A.M. Mech. Dev. 1997; 61: 151-163Crossref PubMed Scopus (133) Google Scholar). In adult myofibers myoD is thought to mediate innervation and thyroid hormone effects on fiber type-specific gene expression (26Hughes S.M. Taylor J.M. Tapscott S.J. Gurley C.M. Carter W.J. Peterson C.A. Development. 1993; 118: 1137-1147Crossref PubMed Google Scholar) as well as repress slow isoform gene function (28Goblet C. Whalen R.G. Dev. Biol. 1995; 170: 262-273Crossref PubMed Scopus (27) Google Scholar). Other genes that are specific to fast glycolytic fiber include myosin heavy chain 2B (MyHC 2B) (reviewed in Ref. 29Schiaffino S. Reggiani C. Physiol. Rev. 1996; 76: 371-423Crossref PubMed Scopus (1263) Google Scholar) and a muscle-specific form of the glycolytic enzyme aldolase A (M-aldA) (30Colbert M.C. Ciejeck-Baez E. Dev. Biol. 1992; 149: 66-79Crossref PubMed Scopus (10) Google Scholar). Therefore, striamin may function as a mediator of extrinsic factors on gene expression in fast glycolytic fibers, as a determinant of metabolism, or as a determinant of muscle contractile activity.Adult skeletal muscle can undergo regeneration, repair, and growth in response to injury or various stresses (31Antonio J. Gonyea W.J. Med. Sci. Sports Exercise. 1993; 25: 1333-1345Crossref PubMed Scopus (2) Google Scholar, 32Grounds M.D. Yablonka-Reuveni Z. Partridge T. Molecular and Cell Biology of Muscular Dystrophy. Chapman & Hall, London1993: 210-256Crossref Scopus (170) Google Scholar). These processes are achieved by the activation of muscle precursor or satellite cells. In normal skeletal muscle, satellite cells are mitotically quiescent, mononucleated cells that are situated between the basement membrane and the myofiber plasma membrane. Injury or stress results in the mitotic activation of the satellite cells, which proliferate and fuse to repair damaged fibers or increase the size of existing fibers. The progression from proliferating to fusion competent satellite cells is marked by a precise order of expression of myogenic regulatory factors and muscle structural proteins. This includes, in order, MyoD, myogenin, α-smooth muscle actin, and sarcomeric myosin (33Yablonka-Reuveni Z. Rivera A.J. Dev. Biol. 1994; 164: 588-603Crossref PubMed Scopus (349) Google Scholar). Becausestriamin is expressed in myoblasts in culture, it is a candidate marker for activated satellite cells and may play a role in the differentiation process in vivo.striamin is expressed in mouse, but not in human, heart. Differences exist between rodent and human cardiac myofibers in contraction velocities and force production, which in large part reflects the ATPase activity conferred by the MyHC isoform present (34Swynghedauw B. Physiol. Rev. 1996; 66: 710-771Crossref Scopus (526) Google Scholar). α-MyHC, the predominant isoform in the rodent heart, confers a faster shortening velocity and low efficiency of force production. In contrast, β-MyHC predominates in the human heart, which has a slower shortening velocity and high efficiency of force production. Rodent and human hearts also differ in the relative amounts of sarcomeric actins present, cardiac and skeletal actin (35Gunning P. Ponte P. Blau H. Kedes L. Mol. Cell. Biol. 1983; 3: 1985-1995Crossref PubMed Google Scholar, 36Boheler K.R. Carrier L. de la Bastie D. Allen P.D. Komajda M. Mercadier J.-J. Schwartz K. J. Clin. Invest. 1991; 88: 323-330Crossref PubMed Scopus (101) Google Scholar), which most likely reflects a difference in force development (37Hewett T.E. Grupp I.L. Grupp G. Robbins J. Circ. Res. 1994; 74: 740-746Crossref PubMed Scopus (120) Google Scholar). The combinations of MyHCs and sarcomeric actins in rodent versus human heart results in a rodent heart that is more similar in contractile properties to a fast-twitch skeletal muscle fiber, whereas the opposite is true for the human heart. Therefore, the expression ofstriamin in striated muscles and mouse heart is consistent with a role in a fast contractile phenotype.striamin Was Found to Interact with p53 in Vitro and in VivoRepression of p53 activity by striamin is consistent with its down-regulation during in vitromyogenesis when significant increase in p53 activity has been reported (22Prokocimer M. Rotter V. Blood. 1994; 84: 2391-2411Crossref PubMed Google Scholar). These data suggests that striamin may affect myogenesis via a direct interaction with p53. Our data suggested that both the N- and C-terminal halves of striamin protein can bind to p53; however, it is the C terminus of striamin that represses transcriptional activity of p53. This suggests that there are more than one p53 binding sites in striamin protein andvice versa. Characterization of these warrant further studies.The myogenic differentiation program includes activation of myogenic transcription factors, intercellular fusion of myoblasts, their withdrawal from the cell cycle, and terminal differentiation to myotubes. Besides the muscle-specific family of transcription factors, myoD family, several adhesion molecules such as N-CAM, N-cadherin, very late activation antigen 4, vascular cell adhesion molecule 1 (VCAM-1), and meltrin-α have been implicated in this process (38Dickson G. Peck D. Moore S.E. Barton C.H. Walsh F.S. Nature. 1990; 344: 348-351Crossref PubMed Scopus (112) Google Scholar, 39Knudsen K.A. McElwee S.A. Myers L. Dev. Biol. 1990; 138: 159-168Crossref PubMed Scopus (93) Google Scholar, 40Rosen G.D. Sanes J.R. LaChance R. Cunningham J.M. Roman J. Dean D.C. Cell. 1992; 69: 1107-1119Abstract Full Text PDF PubMed Scopus (315) Google Scholar, 41Yagami-Hiromasa T. Sato T. Kurisaki T. Kamijo K. Nabeshima Y. Fujisawa-Sehara A. Nature. 1995; 377: 652-656Crossref PubMed Scopus (438) Google Scholar). Bone morphogenetic protein-12 and -13, TGF-β, and other members of the TGF-β superfamily (42Inada M. Katagiri T. Akiyama S. Namiki M. Komaki M. Yamaguchi A. Kamoi K. Rosen V. Suda T. Biochem. Biophys. Res. Commun. 1996; 222: 317-322Crossref PubMed Scopus (55) Google Scholar, 43Filvaroff E.H. Ebner R. Derynck R. Development. 1994; 120: 1085-1095PubMed Google Scholar), ERK-6, a mitogen-activated protein kinase (44Lechner C. Zahalka M.A. Giot J.F. Moller N.P.H. Ullrich A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 4355-4359Crossref PubMed Scopus (274) Google Scholar), and PAX3 (45Epstein J.A. Lam P. Jepeal L. Maas R.L. Shapiro D.N. J. Biol. Chem. 1995; 270: 11719-11722Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar) have been shown to interfere with or suppressin vitro myogenesis of C2C12 myoblasts. Cyclin D1 is found to be down regulated with myogenesis of C2C12, in contrast to cyclin D2, which showed transient increase, and cyclin D3, which showed 20-fold increase (7Kiess M. Gill R.M. Hamel P.A. Oncogene. 1995; 10: 159-166PubMed Google Scholar, 46Rao S.S. Kohtz D.S. J. Biol. Chem. 1995; 270: 4093-4100Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar). striamin does not show any structural homology to any of these proteins that have been implicated in different aspects of muscle differentiation. Of particular interest are its fast fiber specificity, nuclear localization, down-regulation with myogenic differentiation, and functional interactions with the tumor suppressor p53, which may predict it to be an important gene in the regulation of the myogenic differentiation program and warrant further studies to elucidate its role in myogenesis and the fast contractile phenotype. Several genes, such as muscle creatine kinase, troponins, caveolin-3, α-actin, and myosin, have been reported to be predominantly expressed in skeletal muscle. A family of muscle-specific transcription factors such as myoD, myogenin, myf-5, and MRF-4/herculin/myf-6 that regulate muscle-specific gene expression has also been cloned. These are phosphorylated nuclear proteins, containing helix-loop-helix motifs required for dimerization and DNA binding, that can determine a specific cellular differentiation program (1Olson E.N. Klein W.H. Genes Dev. 1994; 8: 1-8Crossref PubMed Scopus (606) Google Scholar). The myoD family of transcription factors has been shown to direct myogenesis, repress proliferation, activate differentiation, and induce contractile phenotypes. The introduction of any one of these into nonmyogenic cells induces their differentiation into mature muscle cells (2Weintraub H. Davis R. Tapscott S. Thayer M. Krause M. Benezra R. Blackwell T.K. Turner D. Rupp R. Hollenberg S. Zhuang Y. Lassar A.B. Science. 1991; 251: 761-766Crossref PubMed Scopus (1226) Google Scholar). The MyoD and myf-5 are expressed in proliferating myoblasts whereas myogenin and MRF-4 are not expressed until myoblasts exit the cell cycle in response to mitogen depletion. Therefore, myoD and myf-5 have been im- plicated as having a role in proliferating myoblasts whereas myogenin and MRF-4 have been shown to activate and maintain muscle gene expression (3Emerson C.P.J. Curr. Opin. Cell Biol. 1993; 5: 1057-1064Crossref PubMed Scopus (34) Google Scholar). In addition, the cell cycle regulatory proteins such as RB (4Shiio Y. Sawada J.I. Handa H. Yamamoto T. Inoue J.I. Oncogene. 1996; 12: 1837-1845PubMed Google Scholar, 5Wang J. Guo K. Wills K.N. Walsh K. Cancer Res. 1997; 57: 351-354PubMed Google Scholar), p21 (6Guo K. Wang J. Andres V. Smith R.C. Walsh K. Mol. Cell. Biol. 1995; 15: 3823-3829Crossref PubMed Scopus (361) Google Scholar), cyclin D, cdk2, cdk4 (7Kiess M. Gill R.M. Hamel P.A. Oncogene. 1995; 10: 159-166PubMed Google Scholar), and p53 (8Soddu S. Blandino G. Scardigli R. Coen S. Marchetti A. Rizzo M.G. Bossi G. Cimino L. Crescenzi M. Sacchi A. J. Cell Biol. 1996; 134: 193-204Crossref PubMed Scopus (121) Google Scholar) have been implicated in the muscle differentiation program. Recently, caveolin-3, α-dystroglycan, and DNA methyltransferase (9Song K.S. Scherer P.E Tang Z. Okamoto T. Li S. Chafel M. Chu D. Kohtz D.S. Lisanti M.P. J. Cell Biol. 1996; 271: 15160-15165Scopus (606) Google Scholar, 10Kostrominova T.Y. Tanzer M.L. J. Cell. Biochem. 1995; 58: 527-534Crossref PubMed Scopus (21) Google Scholar, 11Takagi H. Tajima S. Asano A. Eur. J. Biochem. 1995; 231: 282-291Crossref PubMed Scopus (47) Google Scholar) have also been assigned a positive role in myogenic differentiation. While looking for genes involved in senescence and immortalization, we fortuitously cloned a novel gene that is specifically expressed in fast twitch skeletal muscles. The gene is named “striamin” because of its specific expression in striated muscle. Cloning of the cDNA, expression analyses, subcellular localization, chromosomal assignment, its interactions with the tumor suppressor p53, and its possible significance during muscle differentiation are reported herein. DISCUSSIONHere we report cloning and characterization of a novel gene,striamin, whose expression is restricted to the striated muscles. The expression pattern of striamin shares features in common with a few other genes, but is most similar to that of MyoD. Both are expressed in proliferating myoblasts, decline during differentiation, and yet are present in adult skeletal muscle (26Hughes S.M. Taylor J.M. Tapscott S.J. Gurley C.M. Carter W.J. Peterson C.A. Development. 1993; 118: 1137-1147Crossref PubMed Google Scholar). Furthermore, they appear to be preferentially expressed in fast glycolytic muscle fibers in the adult mouse (27Hughes S.M. Koishi K. Rudnicki M. Maggs A.M. Mech. Dev. 1997; 61: 151-163Crossref PubMed Scopus (133) Google Scholar). In adult myofibers myoD is thought to mediate innervation and thyroid hormone effects on fiber type-specific gene expression (26Hughes S.M. Taylor J.M. Tapscott S.J. Gurley C.M. Carter W.J. Peterson C.A. Development. 1993; 118: 1137-1147Crossref PubMed Google Scholar) as well as repress slow isoform gene function (28Goblet C. Whalen R.G. Dev. Biol. 1995; 170: 262-273Crossref PubMed Scopus (27) Google Scholar). Other genes that are specific to fast glycolytic fiber include myosin heavy chain 2B (MyHC 2B) (reviewed in Ref. 29Schiaffino S. Reggiani C. Physiol. Rev. 1996; 76: 371-423Crossref PubMed Scopus (1263) Google Scholar) and a muscle-specific form of the glycolytic enzyme aldolase A (M-aldA) (30Colbert M.C. Ciejeck-Baez E. Dev. Biol. 1992; 149: 66-79Crossref PubMed Scopus (10) Google Scholar). Therefore, striamin may function as a mediator of extrinsic factors on gene expression in fast glycolytic fibers, as a determinant of metabolism, or as a determinant of muscle contractile activity.Adult skeletal muscle can undergo regeneration, repair, and growth in response to injury or various stresses (31Antonio J. Gonyea W.J. Med. Sci. Sports Exercise. 1993; 25: 1333-1345Crossref PubMed Scopus (2) Google Scholar, 32Grounds M.D. Yablonka-Reuveni Z. Partridge T. Molecular and Cell Biology of Muscular Dystrophy. Chapman & Hall, London1993: 210-256Crossref Scopus (170) Google Scholar). These processes are achieved by the activation of muscle precursor or satellite cells. In normal skeletal muscle, satellite cells are mitotically quiescent, mononucleated cells that are situated between the basement membrane and the myofiber plasma membrane. Injury or stress results in the mitotic activation of the satellite cells, which proliferate and fuse to repair damaged fibers or increase the size of existing fibers. The progression from proliferating to fusion competent satellite cells is marked by a precise order of expression of myogenic regulatory factors and muscle structural proteins. This includes, in order, MyoD, myogenin, α-smooth muscle actin, and sarcomeric myosin (33Yablonka-Reuveni Z. Rivera A.J. Dev. Biol. 1994; 164: 588-603Crossref PubMed Scopus (349) Google Scholar). Becausestriamin is expressed in myoblasts in culture, it is a candidate marker for activated satellite cells and may play a role in the differentiation process in vivo.striamin is expressed in mouse, but not in human, heart. Differences exist between rodent and human cardiac myofibers in contraction velocities and force production, which in large part reflects the ATPase activity conferred by the MyHC isoform present (34Swynghedauw B. Physiol. Rev. 1996; 66: 710-771Crossref Scopus (526) Google Scholar). α-MyHC, the predominant isoform in the rodent heart, confers a faster shortening velocity and low efficiency of force production. In contrast, β-MyHC predominates in the human heart, which has a slower shortening velocity and high efficiency of force production. Rodent and human hearts also differ in the relative amounts of sarcomeric actins present, cardiac and skeletal actin (35Gunning P. Ponte P. Blau H. Kedes L. Mol. Cell. Biol. 1983; 3: 1985-1995Crossref PubMed Google Scholar, 36Boheler K.R. Carrier L. de la Bastie D. Allen P.D. Komajda M. Mercadier J.-J. Schwartz K. J. Clin. Invest. 1991; 88: 323-330Crossref PubMed Scopus (101) Google Scholar), which most likely reflects a difference in force development (37Hewett T.E. Grupp I.L. Grupp G. Robbins J. Circ. Res. 1994; 74: 740-746Crossref PubMed Scopus (120) Google Scholar). The combinations of MyHCs and sarcomeric actins in rodent versus human heart results in a rodent heart that is more similar in contractile properties to a fast-twitch skeletal muscle fiber, whereas the opposite is true for the human heart. Therefore, the expression ofstriamin in striated muscles and mouse heart is consistent with a role in a fast contractile phenotype.striamin Was Found to Interact with p53 in Vitro and in VivoRepression of p53 activity by striamin is consistent with its down-regulation during in vitromyogenesis when significant increase in p53 activity has been reported (22Prokocimer M. Rotter V. Blood. 1994; 84: 2391-2411Crossref PubMed Google Scholar). These data suggests that striamin may affect myogenesis via a direct interaction with p53. Our data suggested that both the N- and C-terminal halves of striamin protein can bind to p53; however, it is the C terminus of striamin that represses transcriptional activity of p53. This suggests that there are more than one p53 binding sites in striamin protein andvice versa. Characterization of these warrant further studies.The myogenic differentiation program includes activation of myogenic transcription factors, intercellular fusion of myoblasts, their withdrawal from the cell cycle, and terminal differentiation to myotubes. Besides the muscle-specific family of transcription factors, myoD family, several adhesion molecules such as N-CAM, N-cadherin, very late activation antigen 4, vascular cell adhesion molecule 1 (VCAM-1), and meltrin-α have been implicated in this process (38Dickson G. Peck D. Moore S.E. Barton C.H. Walsh F.S. Nature. 1990; 344: 348-351Crossref PubMed Scopus (112) Google Scholar, 39Knudsen K.A. McElwee S.A. Myers L. Dev. Biol. 1990; 138: 159-168Crossref PubMed Scopus (93) Google Scholar, 40Rosen G.D. Sanes J.R. LaChance R. Cunningham J.M. Roman J. Dean D.C. Cell. 1992; 69: 1107-1119Abstract Full Text PDF PubMed Scopus (315) Google Scholar, 41Yagami-Hiromasa T. Sato T. Kurisaki T. Kamijo K. Nabeshima Y. Fujisawa-Sehara A. Nature. 1995; 377: 652-656Crossref PubMed Scopus (438) Google Scholar). Bone morphogenetic protein-12 and -13, TGF-β, and other members of the TGF-β superfamily (42Inada M. Katagiri T. Akiyama S. Namiki M. Komaki M. Yamaguchi A. Kamoi K. Rosen V. Suda T. Biochem. Biophys. Res. Commun. 1996; 222: 317-322Crossref PubMed Scopus (55) Google Scholar, 43Filvaroff E.H. Ebner R. Derynck R. Development. 1994; 120: 1085-1095PubMed Google Scholar), ERK-6, a mitogen-activated protein kinase (44Lechner C. Zahalka M.A. Giot J.F. Moller N.P.H. Ullrich A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 4355-4359Crossref PubMed Scopus (274) Google Scholar), and PAX3 (45Epstein J.A. Lam P. Jepeal L. Maas R.L. Shapiro D.N. J. Biol. Chem. 1995; 270: 11719-11722Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar) have been shown to interfere with or suppressin vitro myogenesis of C2C12 myoblasts. Cyclin D1 is found to be down regulated with myogenesis of C2C12, in contrast to cyclin D2, which showed transient increase, and cyclin D3, which showed 20-fold increase (7Kiess M. Gill R.M. Hamel P.A. Oncogene. 1995; 10: 159-166PubMed Google Scholar, 46Rao S.S. Kohtz D.S. J. Biol. Chem. 1995; 270: 4093-4100Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar). striamin does not show any structural homology to any of these proteins that have been implicated in different aspects of muscle differentiation. Of particular interest are its fast fiber specificity, nuclear localization, down-regulation with myogenic differentiation, and functional interactions with the tumor suppressor p53, which may predict it to be an important gene in the regulation of the myogenic differentiation program and warrant further studies to elucidate its role in myogenesis and the fast contractile phenotype. Here we report cloning and characterization of a novel gene,striamin, whose expression is restricted to the striated muscles. The expression pattern of striamin shares features in common with a few other genes, but is most similar to that of MyoD. Both are expressed in proliferating myoblasts, decline during differentiation, and yet are present in adult skeletal muscle (26Hughes S.M. Taylor J.M. Tapscott S.J. Gurley C.M. Carter W.J. Peterson C.A. Development. 1993; 118: 1137-1147Crossref PubMed Google Scholar). Furthermore, they appear to be preferentially expressed in fast glycolytic muscle fibers in the adult mouse (27Hughes S.M. Koishi K. Rudnicki M. Maggs A.M. Mech. Dev. 1997; 61: 151-163Crossref PubMed Scopus (133) Google Scholar). In adult myofibers myoD is thought to mediate innervation and thyroid hormone effects on fiber type-specific gene expression (26Hughes S.M. Taylor J.M. Tapscott S.J. Gurley C.M. Carter W.J. Peterson C.A. Development. 1993; 118: 1137-1147Crossref PubMed Google Scholar) as well as repress slow isoform gene function (28Goblet C. Whalen R.G. Dev. Biol. 1995; 170: 262-273Crossref PubMed Scopus (27) Google Scholar). Other genes that are specific to fast glycolytic fiber include myosin heavy chain 2B (MyHC 2B) (reviewed in Ref. 29Schiaffino S. Reggiani C. Physiol. Rev. 1996; 76: 371-423Crossref PubMed Scopus (1263) Google Scholar) and a muscle-specific form of the glycolytic enzyme aldolase A (M-aldA) (30Colbert M.C. Ciejeck-Baez E. Dev. Biol. 1992; 149: 66-79Crossref PubMed Scopus (10) Google Scholar). Therefore, striamin may function as a mediator of extrinsic factors on gene expression in fast glycolytic fibers, as a determinant of metabolism, or as a determinant of muscle contractile activity. Adult skeletal muscle can undergo regeneration, repair, and growth in response to injury or various stresses (31Antonio J. Gonyea W.J. Med. Sci. Sports Exercise. 1993; 25: 1333-1345Crossref PubMed Scopus (2) Google Scholar, 32Grounds M.D. Yablonka-Reuveni Z. Partridge T. Molecular and Cell Biology of Muscular Dystrophy. Chapman & Hall, London1993: 210-256Crossref Scopus (170) Google Scholar). These processes are achieved by the activation of muscle precursor or satellite cells. In normal skeletal muscle, satellite cells are mitotically quiescent, mononucleated cells that are situated between the basement membrane and the myofiber plasma membrane. Injury or stress results in the mitotic activation of the satellite cells, which proliferate and fuse to repair damaged fibers or increase the size of existing fibers. The progression from proliferating to fusion competent satellite cells is marked by a precise order of expression of myogenic regulatory factors and muscle structural proteins. This includes, in order, MyoD, myogenin, α-smooth muscle actin, and sarcomeric myosin (33Yablonka-Reuveni Z. Rivera A.J. Dev. Biol. 1994; 164: 588-603Crossref PubMed Scopus (349) Google Scholar). Becausestriamin is expressed in myoblasts in culture, it is a candidate marker for activated satellite cells and may play a role in the differentiation process in vivo. striamin is expressed in mouse, but not in human, heart. Differences exist between rodent and human cardiac myofibers in contraction velocities and force production, which in large part reflects the ATPase activity conferred by the MyHC isoform present (34Swynghedauw B. Physiol. Rev. 1996; 66: 710-771Crossref Scopus (526) Google Scholar). α-MyHC, the predominant isoform in the rodent heart, confers a faster shortening velocity and low efficiency of force production. In contrast, β-MyHC predominates in the human heart, which has a slower shortening velocity and high efficiency of force production. Rodent and human hearts also differ in the relative amounts of sarcomeric actins present, cardiac and skeletal actin (35Gunning P. Ponte P. Blau H. Kedes L. Mol. Cell. Biol. 1983; 3: 1985-1995Crossref PubMed Google Scholar, 36Boheler K.R. Carrier L. de la Bastie D. Allen P.D. Komajda M. Mercadier J.-J. Schwartz K. J. Clin. Invest. 1991; 88: 323-330Crossref PubMed Scopus (101) Google Scholar), which most likely reflects a difference in force development (37Hewett T.E. Grupp I.L. Grupp G. Robbins J. Circ. Res. 1994; 74: 740-746Crossref PubMed Scopus (120) Google Scholar). The combinations of MyHCs and sarcomeric actins in rodent versus human heart results in a rodent heart that is more similar in contractile properties to a fast-twitch skeletal muscle fiber, whereas the opposite is true for the human heart. Therefore, the expression ofstriamin in striated muscles and mouse heart is consistent with a role in a fast contractile phenotype. striamin Was Found to Interact with p53 in Vitro and in VivoRepression of p53 activity by striamin is consistent with its down-regulation during in vitromyogenesis when significant increase in p53 activity has been reported (22Prokocimer M. Rotter V. Blood. 1994; 84: 2391-2411Crossref PubMed Google Scholar). These data suggests that striamin may affect myogenesis via a direct interaction with p53. Our data suggested that both the N- and C-terminal halves of striamin protein can bind to p53; however, it is the C terminus of striamin that represses transcriptional activity of p53. This suggests that there are more than one p53 binding sites in striamin protein andvice versa. Characterization of these warrant further studies.The myogenic differentiation program includes activation of myogenic transcription factors, intercellular fusion of myoblasts, their withdrawal from the cell cycle, and terminal differentiation to myotubes. Besides the muscle-specific family of transcription factors, myoD family, several adhesion molecules such as N-CAM, N-cadherin, very late activation antigen 4, vascular cell adhesion molecule 1 (VCAM-1), and meltrin-α have been implicated in this process (38Dickson G. Peck D. Moore S.E. Barton C.H. Walsh F.S. Nature. 1990; 344: 348-351Crossref PubMed Scopus (112) Google Scholar, 39Knudsen K.A. McElwee S.A. Myers L. Dev. Biol. 1990; 138: 159-168Crossref PubMed Scopus (93) Google Scholar, 40Rosen G.D. Sanes J.R. LaChance R. Cunningham J.M. Roman J. Dean D.C. Cell. 1992; 69: 1107-1119Abstract Full Text PDF PubMed Scopus (315) Google Scholar, 41Yagami-Hiromasa T. Sato T. Kurisaki T. Kamijo K. Nabeshima Y. Fujisawa-Sehara A. Nature. 1995; 377: 652-656Crossref PubMed Scopus (438) Google Scholar). Bone morphogenetic protein-12 and -13, TGF-β, and other members of the TGF-β superfamily (42Inada M. Katagiri T. Akiyama S. Namiki M. Komaki M. Yamaguchi A. Kamoi K. Rosen V. Suda T. Biochem. Biophys. Res. Commun. 1996; 222: 317-322Crossref PubMed Scopus (55) Google Scholar, 43Filvaroff E.H. Ebner R. Derynck R. Development. 1994; 120: 1085-1095PubMed Google Scholar), ERK-6, a mitogen-activated protein kinase (44Lechner C. Zahalka M.A. Giot J.F. Moller N.P.H. Ullrich A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 4355-4359Crossref PubMed Scopus (274) Google Scholar), and PAX3 (45Epstein J.A. Lam P. Jepeal L. Maas R.L. Shapiro D.N. J. Biol. Chem. 1995; 270: 11719-11722Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar) have been shown to interfere with or suppressin vitro myogenesis of C2C12 myoblasts. Cyclin D1 is found to be down regulated with myogenesis of C2C12, in contrast to cyclin D2, which showed transient increase, and cyclin D3, which showed 20-fold increase (7Kiess M. Gill R.M. Hamel P.A. Oncogene. 1995; 10: 159-166PubMed Google Scholar, 46Rao S.S. Kohtz D.S. J. Biol. Chem. 1995; 270: 4093-4100Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar). striamin does not show any structural homology to any of these proteins that have been implicated in different aspects of muscle differentiation. Of particular interest are its fast fiber specificity, nuclear localization, down-regulation with myogenic differentiation, and functional interactions with the tumor suppressor p53, which may predict it to be an important gene in the regulation of the myogenic differentiation program and warrant further studies to elucidate its role in myogenesis and the fast contractile phenotype. striamin Was Found to Interact with p53 in Vitro and in VivoRepression of p53 activity by striamin is consistent with its down-regulation during in vitromyogenesis when significant increase in p53 activity has been reported (22Prokocimer M. Rotter V. Blood. 1994; 84: 2391-2411Crossref PubMed Google Scholar). These data suggests that striamin may affect myogenesis via a direct interaction with p53. Our data suggested that both the N- and C-terminal halves of striamin protein can bind to p53; however, it is the C terminus of striamin that represses transcriptional activity of p53. This suggests that there are more than one p53 binding sites in striamin protein andvice versa. Characterization of these warrant further studies.The myogenic differentiation program includes activation of myogenic transcription factors, intercellular fusion of myoblasts, their withdrawal from the cell cycle, and terminal differentiation to myotubes. Besides the muscle-specific family of transcription factors, myoD family, several adhesion molecules such as N-CAM, N-cadherin, very late activation antigen 4, vascular cell adhesion molecule 1 (VCAM-1), and meltrin-α have been implicated in this process (38Dickson G. Peck D. Moore S.E. Barton C.H. Walsh F.S. Nature. 1990; 344: 348-351Crossref PubMed Scopus (112) Google Scholar, 39Knudsen K.A. McElwee S.A. Myers L. Dev. Biol. 1990; 138: 159-168Crossref PubMed Scopus (93) Google Scholar, 40Rosen G.D. Sanes J.R. LaChance R. Cunningham J.M. Roman J. Dean D.C. Cell. 1992; 69: 1107-1119Abstract Full Text PDF PubMed Scopus (315) Google Scholar, 41Yagami-Hiromasa T. Sato T. Kurisaki T. Kamijo K. Nabeshima Y. Fujisawa-Sehara A. Nature. 1995; 377: 652-656Crossref PubMed Scopus (438) Google Scholar). Bone morphogenetic protein-12 and -13, TGF-β, and other members of the TGF-β superfamily (42Inada M. Katagiri T. Akiyama S. Namiki M. Komaki M. Yamaguchi A. Kamoi K. Rosen V. Suda T. Biochem. Biophys. Res. Commun. 1996; 222: 317-322Crossref PubMed Scopus (55) Google Scholar, 43Filvaroff E.H. Ebner R. Derynck R. Development. 1994; 120: 1085-1095PubMed Google Scholar), ERK-6, a mitogen-activated protein kinase (44Lechner C. Zahalka M.A. Giot J.F. Moller N.P.H. Ullrich A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 4355-4359Crossref PubMed Scopus (274) Google Scholar), and PAX3 (45Epstein J.A. Lam P. Jepeal L. Maas R.L. Shapiro D.N. J. Biol. Chem. 1995; 270: 11719-11722Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar) have been shown to interfere with or suppressin vitro myogenesis of C2C12 myoblasts. Cyclin D1 is found to be down regulated with myogenesis of C2C12, in contrast to cyclin D2, which showed transient increase, and cyclin D3, which showed 20-fold increase (7Kiess M. Gill R.M. Hamel P.A. Oncogene. 1995; 10: 159-166PubMed Google Scholar, 46Rao S.S. Kohtz D.S. J. Biol. Chem. 1995; 270: 4093-4100Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar). striamin does not show any structural homology to any of these proteins that have been implicated in different aspects of muscle differentiation. Of particular interest are its fast fiber specificity, nuclear localization, down-regulation with myogenic differentiation, and functional interactions with the tumor suppressor p53, which may predict it to be an important gene in the regulation of the myogenic differentiation program and warrant further studies to elucidate its role in myogenesis and the fast contractile phenotype. striamin Was Found to Interact with p53 in Vitro and in VivoRepression of p53 activity by striamin is consistent with its down-regulation during in vitromyogenesis when significant increase in p53 activity has been reported (22Prokocimer M. Rotter V. Blood. 1994; 84: 2391-2411Crossref PubMed Google Scholar). These data suggests that striamin may affect myogenesis via a direct interaction with p53. Our data suggested that both the N- and C-terminal halves of striamin protein can bind to p53; however, it is the C terminus of striamin that represses transcriptional activity of p53. This suggests that there are more than one p53 binding sites in striamin protein andvice versa. Characterization of these warrant further studies.The myogenic differentiation program includes activation of myogenic transcription factors, intercellular fusion of myoblasts, their withdrawal from the cell cycle, and terminal differentiation to myotubes. Besides the muscle-specific family of transcription factors, myoD family, several adhesion molecules such as N-CAM, N-cadherin, very late activation antigen 4, vascular cell adhesion molecule 1 (VCAM-1), and meltrin-α have been implicated in this process (38Dickson G. Peck D. Moore S.E. Barton C.H. Walsh F.S. Nature. 1990; 344: 348-351Crossref PubMed Scopus (112) Google Scholar, 39Knudsen K.A. McElwee S.A. Myers L. Dev. Biol. 1990; 138: 159-168Crossref PubMed Scopus (93) Google Scholar, 40Rosen G.D. Sanes J.R. LaChance R. Cunningham J.M. Roman J. Dean D.C. Cell. 1992; 69: 1107-1119Abstract Full Text PDF PubMed Scopus (315) Google Scholar, 41Yagami-Hiromasa T. Sato T. Kurisaki T. Kamijo K. Nabeshima Y. Fujisawa-Sehara A. Nature. 1995; 377: 652-656Crossref PubMed Scopus (438) Google Scholar). Bone morphogenetic protein-12 and -13, TGF-β, and other members of the TGF-β superfamily (42Inada M. Katagiri T. Akiyama S. Namiki M. Komaki M. Yamaguchi A. Kamoi K. Rosen V. Suda T. Biochem. Biophys. Res. Commun. 1996; 222: 317-322Crossref PubMed Scopus (55) Google Scholar, 43Filvaroff E.H. Ebner R. Derynck R. Development. 1994; 120: 1085-1095PubMed Google Scholar), ERK-6, a mitogen-activated protein kinase (44Lechner C. Zahalka M.A. Giot J.F. Moller N.P.H. Ullrich A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 4355-4359Crossref PubMed Scopus (274) Google Scholar), and PAX3 (45Epstein J.A. Lam P. Jepeal L. Maas R.L. Shapiro D.N. J. Biol. Chem. 1995; 270: 11719-11722Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar) have been shown to interfere with or suppressin vitro myogenesis of C2C12 myoblasts. Cyclin D1 is found to be down regulated with myogenesis of C2C12, in contrast to cyclin D2, which showed transient increase, and cyclin D3, which showed 20-fold increase (7Kiess M. Gill R.M. Hamel P.A. Oncogene. 1995; 10: 159-166PubMed Google Scholar, 46Rao S.S. Kohtz D.S. J. Biol. Chem. 1995; 270: 4093-4100Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar). striamin does not show any structural homology to any of these proteins that have been implicated in different aspects of muscle differentiation. Of particular interest are its fast fiber specificity, nuclear localization, down-regulation with myogenic differentiation, and functional interactions with the tumor suppressor p53, which may predict it to be an important gene in the regulation of the myogenic differentiation program and warrant further studies to elucidate its role in myogenesis and the fast contractile phenotype. Repression of p53 activity by striamin is consistent with its down-regulation during in vitromyogenesis when significant increase in p53 activity has been reported (22Prokocimer M. Rotter V. Blood. 1994; 84: 2391-2411Crossref PubMed Google Scholar). These data suggests that striamin may affect myogenesis via a direct interaction with p53. Our data suggested that both the N- and C-terminal halves of striamin protein can bind to p53; however, it is the C terminus of striamin that represses transcriptional activity of p53. This suggests that there are more than one p53 binding sites in striamin protein andvice versa. Characterization of these warrant further studies. The myogenic differentiation program includes activation of myogenic transcription factors, intercellular fusion of myoblasts, their withdrawal from the cell cycle, and terminal differentiation to myotubes. Besides the muscle-specific family of transcription factors, myoD family, several adhesion molecules such as N-CAM, N-cadherin, very late activation antigen 4, vascular cell adhesion molecule 1 (VCAM-1), and meltrin-α have been implicated in this process (38Dickson G. Peck D. Moore S.E. Barton C.H. Walsh F.S. Nature. 1990; 344: 348-351Crossref PubMed Scopus (112) Google Scholar, 39Knudsen K.A. McElwee S.A. Myers L. Dev. Biol. 1990; 138: 159-168Crossref PubMed Scopus (93) Google Scholar, 40Rosen G.D. Sanes J.R. LaChance R. Cunningham J.M. Roman J. Dean D.C. Cell. 1992; 69: 1107-1119Abstract Full Text PDF PubMed Scopus (315) Google Scholar, 41Yagami-Hiromasa T. Sato T. Kurisaki T. Kamijo K. Nabeshima Y. Fujisawa-Sehara A. Nature. 1995; 377: 652-656Crossref PubMed Scopus (438) Google Scholar). Bone morphogenetic protein-12 and -13, TGF-β, and other members of the TGF-β superfamily (42Inada M. Katagiri T. Akiyama S. Namiki M. Komaki M. Yamaguchi A. Kamoi K. Rosen V. Suda T. Biochem. Biophys. Res. Commun. 1996; 222: 317-322Crossref PubMed Scopus (55) Google Scholar, 43Filvaroff E.H. Ebner R. Derynck R. Development. 1994; 120: 1085-1095PubMed Google Scholar), ERK-6, a mitogen-activated protein kinase (44Lechner C. Zahalka M.A. Giot J.F. Moller N.P.H. Ullrich A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 4355-4359Crossref PubMed Scopus (274) Google Scholar), and PAX3 (45Epstein J.A. Lam P. Jepeal L. Maas R.L. Shapiro D.N. J. Biol. Chem. 1995; 270: 11719-11722Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar) have been shown to interfere with or suppressin vitro myogenesis of C2C12 myoblasts. Cyclin D1 is found to be down regulated with myogenesis of C2C12, in contrast to cyclin D2, which showed transient increase, and cyclin D3, which showed 20-fold increase (7Kiess M. Gill R.M. Hamel P.A. Oncogene. 1995; 10: 159-166PubMed Google Scholar, 46Rao S.S. Kohtz D.S. J. Biol. Chem. 1995; 270: 4093-4100Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar). striamin does not show any structural homology to any of these proteins that have been implicated in different aspects of muscle differentiation. Of particular interest are its fast fiber specificity, nuclear localization, down-regulation with myogenic differentiation, and functional interactions with the tumor suppressor p53, which may predict it to be an important gene in the regulation of the myogenic differentiation program and warrant further studies to elucidate its role in myogenesis and the fast contractile phenotype. We greatly appreciate the kind assistance of John O'Mahoney, Xavier Badoux, and Vicky Ferguson for Northern analysis" @default.
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W1988595972 title "Cloning and Characterization of a Novel Gene,striamin, That Interacts with the Tumor Suppressor Protein p53" @default.
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