FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2002143651> ?p ?o ?g. }

• W2002143651 endingPage "26940" @default.
• W2002143651 startingPage "26928" @default.
• W2002143651 abstract "Y-box (YB) protein-1 is secreted by mesangial and immune cells after cytokine challenge, but extracellular functions are unknown. Here, we demonstrate that extracellular YB-1 associates with outer cell membrane components and interacts with extracellular Notch-3 receptor domains. The interaction appears to be specific for Notch-3, as YB-1-green fluorescent protein binds to the extracellular domains and full-length forms of Notch-3 but not to Notch-1. YB-1-green fluorescent protein and Notch-3 proteins co-localize at cell membranes, and extracellular YB-1 activates Notch-3 signaling, resulting in nuclear translocation of the Notch-3 intracellular domain and up-regulation of Notch target genes. The YB-1/Notch-3 interaction may be of particular relevance for inflammatory mesangioproliferative disease, as both proteins co-localize in an experimental nephritis model and receptor activation temporally and spatially correlates with YB-1 expression. Y-box (YB) protein-1 is secreted by mesangial and immune cells after cytokine challenge, but extracellular functions are unknown. Here, we demonstrate that extracellular YB-1 associates with outer cell membrane components and interacts with extracellular Notch-3 receptor domains. The interaction appears to be specific for Notch-3, as YB-1-green fluorescent protein binds to the extracellular domains and full-length forms of Notch-3 but not to Notch-1. YB-1-green fluorescent protein and Notch-3 proteins co-localize at cell membranes, and extracellular YB-1 activates Notch-3 signaling, resulting in nuclear translocation of the Notch-3 intracellular domain and up-regulation of Notch target genes. The YB-1/Notch-3 interaction may be of particular relevance for inflammatory mesangioproliferative disease, as both proteins co-localize in an experimental nephritis model and receptor activation temporally and spatially correlates with YB-1 expression. The Y-box (YB) 3The abbreviations used are: YBY-boxEGFepidermal growth factorHEKhuman embryonic kidneyTRITCtetramethylrhodamine isothiocyanateHKhuman kidneyCREBcAMP-response element-binding proteinHAhemagglutininIPimmunoprecipitateICN3Notch-3 intracellular domainPDGFplatelet-derived growth factorCADASIL syndromecerebral autosomal-dominant arteriopathy with subcortical infarcts and leukencephalopathyGAPDHglyceraldehyde-3-phosphate dehydrogenasePBSphosphate-buffered salineRIPA bufferradioimmune precipitation assay bufferMCmesangial cellsCSLCBP, Suppressor of Hairless, Lag-1CBPCREB-binding protein. 3The abbreviations used are: YBY-boxEGFepidermal growth factorHEKhuman embryonic kidneyTRITCtetramethylrhodamine isothiocyanateHKhuman kidneyCREBcAMP-response element-binding proteinHAhemagglutininIPimmunoprecipitateICN3Notch-3 intracellular domainPDGFplatelet-derived growth factorCADASIL syndromecerebral autosomal-dominant arteriopathy with subcortical infarcts and leukencephalopathyGAPDHglyceraldehyde-3-phosphate dehydrogenasePBSphosphate-buffered salineRIPA bufferradioimmune precipitation assay bufferMCmesangial cellsCSLCBP, Suppressor of Hairless, Lag-1CBPCREB-binding protein. protein-1 belongs to the cold shock family, which is notable for its conservation throughout evolution (1Kohno K. Izumi H. Uchiumi T. Ashizuka M. Kuwano M. BioEssays. 2003; 25: 691-698Crossref PubMed Scopus (431) Google Scholar). Cold shock proteins play pleiotropic roles in gene regulation, pre-mRNA splicing (2Raffetseder U. Frye B. Rauen T. Jürchott K. Royer H.D. Jansen P.L. Mertens P.R. J. Biol. Chem. 2003; 278: 18241-18248Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar), mRNA translocation, mRNA masking, and mRNA translation (3Evdokimova V. Ruzanov P. Anglesio M.S. Sorokin A.V. Ovchinnikov L.P. Buckley J. Triche T.J. Sonenberg N. Sorensen P.H. Mol. Cell. Biol. 2006; 26: 277-292Crossref PubMed Scopus (213) Google Scholar). The prototypic member YB-1 exhibits an exceptional high degree of phylogenetic conservation not only in the cold shock domain but also throughout the rest of the molecule.The protein may be divided into three distinct domains, the alanine/glycine/proline-rich N-terminal part, the centrally located cold shock domain, and a C-terminal region characterized by four alternating clusters of basic and acidic amino acids. An interaction with actin has been described for the N-terminal domain (4Ruzanov P.V. Evdokimova V.M. Korneeva N.L. Hershey J.W. Ovchinnikov L.P. J. Cell Sci. 1999; 112: 3487-3496PubMed Google Scholar). The cold shock domain contains basic and aromatic amino acids to attract nucleic acid backbones and to associate with DNA or RNA nucleotide bases. It forms an antiparallel β-barrel, enfolding nucleic acids in a chaperone-like manner (1Kohno K. Izumi H. Uchiumi T. Ashizuka M. Kuwano M. BioEssays. 2003; 25: 691-698Crossref PubMed Scopus (431) Google Scholar). The C-terminal region of YB-1 forms a “charged zipper” with motifs that recognize specific RNA hairpins, contribute to DNA/RNA binding, and function as docking site for other proteins.Recent findings link YB-1 with inflammatory diseases. These include allergic asthma (5Capowski E.E. Esnault S. Bhattacharya S. Malter J.S. J. Immunol. 2001; 167: 5970-5976Crossref PubMed Scopus (82) Google Scholar) and mesangioproliferative nephritis, in which YB-1 is a downstream target of cytokine platelet-derived growth factor (PDGF)-BB (6van Roeyen C.R. Eitner F. Martinkus S. Thieltges S.R. Ostendorf T. Bokemeyer D. Lüscher B. Lüscher-Firzlaff J.M. Floege J. Mertens P.R. J. Am. Soc. Nephrol. 2005; 16: 2985-2996Crossref PubMed Scopus (39) Google Scholar), interferon -γ (7Dooley S. Said H.M. Gressner A.M. Floege J. En-Nia A. Mertens P.R. J. Biol. Chem. 2006; 281: 1784-1795Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar), and granulocyte monocyte-colony stimulating factor (5Capowski E.E. Esnault S. Bhattacharya S. Malter J.S. J. Immunol. 2001; 167: 5970-5976Crossref PubMed Scopus (82) Google Scholar). We demonstrated that YB-1 serves as a transcriptional regulator of RANTES (CCL5) expression in atherosclerosis and renal transplant rejection (8Krohn R. Raffetseder U. Bot I. Zernecke A. Shagdarsuren E. Liehn E.A. van Santbrink P.J. Nelson P.J. Biessen E.A. Mertens P.R. Weber C. Circulation. 2007; 116: 1812-1820Crossref PubMed Scopus (77) Google Scholar, 9Raffetseder U. Rauen T. Djudjaj S. Kretzler M. En-Nia A. Tacke F. Zimmermann H.W. Nelson P.J. Frye B.C. Floege J. Stefanidis I. Weber C. Mertens P.R. Kidney Int. 2009; 75: 185-196Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar). There is emerging evidence that YB-1 is also secreted from mesangial and immune cells via a non-classical secretion pathway (10Frye B.C. Halfter S. Djudjaj S. Muehlenberg P. Weber S. Raffetseder U. En-Nia A. Knott H. Baron J.M. Dooley S. Bernhagen J. Mertens P.R. EMBO Rep. 2009; 10: 783-789Crossref PubMed Scopus (91) Google Scholar). To clarify potential extracellular protein functions, we established a two-hybrid screen with YB-1 as bait and searched for interacting proteins. We identified splicing factor SRp30c (2Raffetseder U. Frye B. Rauen T. Jürchott K. Royer H.D. Jansen P.L. Mertens P.R. J. Biol. Chem. 2003; 278: 18241-18248Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar) and a positive clone encoding for the extracellular EGF domains 13–33 of the receptor Notch-3 as potential partner proteins.Notch-3 belongs to a receptor superfamily encompassing Notch-1 through -4 in vertebrates. Notch signaling imparts cell fate decisions in many tissues, including the immune system (11Maillard I. Fang T. Pear W.S. Annu. Rev. Immunol. 2005; 23: 945-974Crossref PubMed Scopus (373) Google Scholar) and vasculo- and organogenesis in multicellular organisms (12Sestan N. Artavanis-Tsakonas S. Rakic P. Science. 1999; 286: 741-746Crossref PubMed Scopus (494) Google Scholar). Notch receptors constitute single-pass transmembrane proteins that contain repetitive epidermal growth factor-like domain repeats (EGF) and three cysteine-rich Notch/Lin-12 repeats within their extracellular domain. The intracellular domain encompasses seven ankyrin repeats, a nuclear localization signal, transcriptional activator domain, and a PEST sequence (13Mertens P.R. Raffetseder U. Rauen T. Nephrol. Dial Transplant. 2008; 23: 2743-2745Crossref PubMed Scopus (17) Google Scholar). Notch receptors are activated by membrane-anchored ligands, like Delta (or Delta-like) and Jagged/Serrate family members, on juxtaposed cells. Upon interaction, two consecutive proteolytic cleavages (S2 and S3) liberate the intracellular Notch receptor domain (ICD), that translocates to the nucleus and acts as a trans-activator of target gene transcription by binding to the DNA-binding protein RBP-Jκ (14Bray S.J. Nat. Rev. Mol. Cell Biol. 2006; 7: 678-689Crossref PubMed Scopus (1932) Google Scholar), which in the absence of Notch ICD acts as a repressor of gene transcription (15Kopan R. Schroeter E.H. Weintraub H. Nye J.S. Proc. Natl. Acad. Sci. U.S.A. 1996; 93: 1683-1688Crossref PubMed Scopus (424) Google Scholar). The basic helix-loop-helix transcription factors HES (Hairy Enhancer of Split) and HERP (HES-related proteins) have been depicted as immediate transcriptional targets of Notch, but an increasing number of further target genes is found.Notch signaling pathways play prominent roles in podocyte development and likely the pathogenesis of diverse glomerular diseases, like diabetic nephropathy and lupus nephritis (16Niranjan T. Bielesz B. Gruenwald A. Ponda M.P. Kopp J.B. Thomas D.B. Susztak K. Nat. Med. 2008; 14: 290-298Crossref PubMed Scopus (319) Google Scholar, 17Teachey D.T. Seif A.E. Brown V.I. Bruno M. Bunte R.M. Chang Y.J. Choi J.K. Fish J.D. Hall J. Reid G.S. Ryan T. Sheen C. Zweidler-McKay P. Grupp S.A. Blood. 2008; 111: 705-714Crossref PubMed Scopus (66) Google Scholar). Deletion of the Notch-2 gene or treatment of developing kidneys with γ-secretase inhibitors leads to severe defects in podocyte and proximal tubule differentiation (18Cheng H.T. Kim M. Valerius M.T. Surendran K. Schuster-Gossler K. Gossler A. McMahon A.P. Kopan R. Development. 2007; 134: 801-811Crossref PubMed Scopus (284) Google Scholar). Furthermore, de novo expression of activated Notch-1 was significantly enhanced in glomerular cells in humans with diabetic nephropathy and focal segmental glomerulosclerosis and rodent models thereof (16Niranjan T. Bielesz B. Gruenwald A. Ponda M.P. Kopp J.B. Thomas D.B. Susztak K. Nat. Med. 2008; 14: 290-298Crossref PubMed Scopus (319) Google Scholar). Whereas insights into the role of Notch receptors in the pathogenesis of human kidney diseases are emerging, there are strong genetic links between mutations within the human Notch-3 gene and a subtype of inherited early-onset dementia (called cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukencephalopathy, CADASIL syndrome) (19Joutel A. Corpechot C. Ducros A. Vahedi K. Chabriat H. Mouton P. Alamowitch S. Domenga V. Cécillion M. Marechal E. Maciazek J. Vayssiere C. Cruaud C. Cabanis E.A. Ruchoux M.M. Weissenbach J. Bach J.F. Bousser M.G. Tournier-Lasserve E. Nature. 1996; 383: 707-710Crossref PubMed Scopus (1667) Google Scholar). Two case reports provide evidence for renal involvement in CADASIL syndrome, namely the coexistence of mesangioproliferative IgA nephritis in kidney biopsies (20Guerrot D. François A. Boffa J.J. Boulos N. Hanoy M. Legallicier B. Triquenot-Bagan A. Guyant-Marechal L. Laquerriere A. Freguin-Bouilland C. Ronco P. Godin M. Am J. Kidney Dis. 2008; 52: 340-345Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 21Kusaba T. Hatta T. Kimura T. Sonomura K. Tanda S. Kishimoto N. Kameyama H. Okigaki M. Mori Y. Ishigami N. Mizuno T. Nakagawa M. Matsubara H. Clin. Nephrol. 2007; 67: 182-187Crossref PubMed Scopus (17) Google Scholar). Given the primary result yielded with the two-hybrid screen, we performed an in-depth analysis of YB-1 association with receptor Notch-3 and potential effects on Notch signaling.DISCUSSIONSecretion of a transcription factor is unexpected at first sight but not unheard of. Similarly to high mobility group box-1 protein (HMGB-1) we determined an active secretion process for YB-1 protein via a non-classical pathway that bypasses the endoplasmic reticulum/Golgi apparatus (10Frye B.C. Halfter S. Djudjaj S. Muehlenberg P. Weber S. Raffetseder U. En-Nia A. Knott H. Baron J.M. Dooley S. Bernhagen J. Mertens P.R. EMBO Rep. 2009; 10: 783-789Crossref PubMed Scopus (91) Google Scholar). In mesangial and inflammatory cells, several cytokines like PDGF-BB, interferon-γ, oxidative stress, and lipopolysaccharide were able to act as secretogogues for YB-1. These findings combined with an observed high affinity of YB-1 for the outer aspect of the cell membrane led us to a search for possible interacting proteins at the cell surface and a two-hybrid screen identified Notch-3 as an interacting protein.This initial finding was corroborated by co-immunoprecipitation and localization studies, which showed that YB-1 interacts with the Notch-3 receptor and that both proteins are found at the cell membrane. Interestingly, co-immunoprecipitation studies demonstrated that the interaction with YB-1 is specific for the Notch-3 receptor, as it does not occur with Notch-1. This was unexpected given the high degree of structural conservation between the two receptors, i.e. the extracellular Notch-3 domains of Notch-1 and Notch-3 are 45% identical, and both are composed of a series of EGF repeats and Notch/Lin-12 repeat regions. Furthermore, Notch-1 and Notch-3 appear to behave very similarly in terms of interaction with the conventional Notch DSL ligands, i.e. Jagged1 and Delta-like-1 (35Sweeney C. Morrow D. Birney Y.A. Coyle S. Hennessy C. Scheller A. Cummins P.M. Walls D. Redmond E.M. Cahill P.A. FASEB J. 2004; 18: 1421-1423Crossref PubMed Scopus (117) Google Scholar). Our data show that the EGF-like repeats 13–33 in Notch-3 are sufficient for interaction with YB-1. This region lies outside the domain previously shown to be required for interaction with DSL ligands, which is confined to EGF-like repeat 11 and 12 (36Rebay I. Fleming R.J. Fehon R.G. Cherbas L. Cherbas P. Artavanis-Tsakonas S. Cell. 1991; 67: 687-699Abstract Full Text PDF PubMed Scopus (596) Google Scholar). The YB-1-interacting domain (EGF-like repeats 13–33) may also be of interest in the context of the Notch 3-associated disease CADASIL. Notch-3 mutations in CADASIL are found in the EGF-like repeats, and several of the observed mutations fall outside the region of DSL ligand interaction but within repeats 13–33, for example, the C542Y and R1006C mutations. Besides the EGF repeats necessary for direct interaction between Notch with DSL ligands, a second functional domain in EGF-repeats 24–29 has been identified in Drosophila melanogaster by a class of Notch missense mutations called Abruptex (Nax). This domain negatively regulates the interaction between Notch and DSL ligands (37de Celis J.F. Bray S.J. Development. 2000; 127: 1291-1302Crossref PubMed Google Scholar), and it has been speculated that it may be necessary to invoke an altered response to a yet unidentified ligand or cofactor. Amino acid substitutions in this domain result in increased Notch activity, presumably by destroying the binding site of the postulated cofactor that functions as a negative regulator (37de Celis J.F. Bray S.J. Development. 2000; 127: 1291-1302Crossref PubMed Google Scholar). Further investigations will be required to verify YB-1 binding to the Abruptex domain and to unravel potential modulating function(s) of YB-1 on DSL ligands.It is of note that the observed receptor activation by YB-1 occurred in the absence of DSL ligand stimulation. The finding of YB-1 as a new ligand for Notch-3 provides further evidence for the existence of “non-conventional” Notch ligands, i.e. ligands that are not part of the DSL family. It has previously been reported that F3/contactin can act as a Notch ligand to control oligodendrocyte differentiation (38Hu Q.D. Ang B.T. Karsak M. Hu W.P. Cui X.Y. Duka T. Takeda Y. Chia W. Sankar N. Ng Y.K. Ling E.A. Maciag T. Small D. Trifonova R. Kopan R. Okano H. Nakafuku M. Chiba S. Hirai H. Aster J.C. Schachner M. Pallen C.J. Watanabe K. Xiao Z.C. Cell. 2003; 115: 163-175Abstract Full Text Full Text PDF PubMed Scopus (298) Google Scholar), and the microfibrillar proteins MAGP1 and MAGP2 were shown to induce Notch-1 signaling (39Miyamoto A. Lau R. Hein P.W. Shipley J.M. Weinmaster G. J. Biol. Chem. 2006; 281: 10089-10097Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar).The Notch receptor signaling invoked by extracellular YB-1 is γ-secretase-dependent and includes HES2 promoter induction. Knowledge on HES2 promoter regulation as part of Notch signaling is rather scarce. Notch receptor-mediated induction of HES2 by membrane-bound ligand Dll4 has been reported (40Scehnet J.S. Jiang W. Kumar S.R. Krasnoperov V. Trindade A. Benedito R. Djokovic D. Borges C. Ley E.J. Duarte A. Gill P.S. Blood. 2007; 109: 4753-4760Crossref PubMed Scopus (216) Google Scholar), and several reports indicate an active role of HES2 in proliferative processes, such as spontaneous malignant transformation of stem cells (41Shiras A. Chettiar S.T. Shepal V. Rajendran G. Prasad G.R. Shastry P. Stem Cells. 2007; 25: 1478-1489Crossref PubMed Scopus (128) Google Scholar) and various tumors, e.g. of the gastrointestinal tract (42Katoh M. Katoh M. Int. J. Oncol. 2007; 31: 461-466PubMed Google Scholar) and Ras-transformed astrocytes (43Kanamori M. Kawaguchi T. Nigro J.M. Feuerstein B.G. Berger M.S. Miele L. Pieper R.O. J. Neurosurg. 2007; 106: 417-427Crossref PubMed Scopus (165) Google Scholar). YB-1 knock-out mice exhibit neural tube defects with abnormal patterns of cell proliferation within the neuroepithelium (44Uchiumi T. Fotovati A. Sasaguri T. Shibahara K. Shimada T. Fukuda T. Nakamura T. Izumi H. Tsuzuki T. Kuwano M. Kohno K. J. Biol. Chem. 2006; 281: 40440-40449Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar). Given the increased HES2 transcript numbers in embryonic neural progenitor cells, one might speculate that YB-1 signaling via Notch-3 constitutes a direct link that is operative in the development of the nervous system.In the present study care was taken to unequivocally demonstrate a direct effect of YB-1 on target gene regulation via the Notch signaling cascade. To this end, two different artificial promoter elements, a concatenated CSL-binding site and a specific promoter for Notch-3 signaling linked to the luciferase gene (MH100), as well as constructs with mutated CSL-binding sites were introduced into HEK293 cells and reproducibly demonstrate activated Notch-3 signaling by extracellular YB-1.It was previously reported that Notch-3 is expressed in adult vascular smooth muscle cells (19Joutel A. Corpechot C. Ducros A. Vahedi K. Chabriat H. Mouton P. Alamowitch S. Domenga V. Cécillion M. Marechal E. Maciazek J. Vayssiere C. Cruaud C. Cabanis E.A. Ruchoux M.M. Weissenbach J. Bach J.F. Bousser M.G. Tournier-Lasserve E. Nature. 1996; 383: 707-710Crossref PubMed Scopus (1667) Google Scholar), which is in keeping with the phenotype in Notch-3-deficient mice. These mice are viable, fertile, and develop largely normally but exhibit problems of vascular smooth muscle cell maturation in distal arteries (45Joutel A. Monet M. Domenga V. Riant F. Tournier-Lasserve E. Am. J. Hum. Genet. 2004; 74: 338-347Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar). Our data show that Notch-3 receptor was detected at the basal membrane of some tubular and collecting duct cells within the inner renal medulla in the adult kidney, whereas no glomerular cells were immunopositive. Subsequent to induction of mesangioproliferative Anti-Thy1.1 nephritis, Notch-3 receptor was detected within the mesangial compartment of glomeruli, and its expression peaked at a time with maximal mesangial cell proliferation rates (29Floege J. Ostendorf T. Janssen U. Burg M. Radeke H.H. Vargeese C. Gill S.C. Green L.S. Janjiæ N. Am J. Pathol. 1999; 154: 169-179Abstract Full Text Full Text PDF PubMed Scopus (221) Google Scholar) and, notably, coincided temporally and spatially with increased glomerular YB-1 protein expression. The presence of cleaved extracellular domains of Notch-3 (ECN3) in the urine of diseased rats underscores its abundant expression and activation in the course of the disease. The band pattern for YB-1 in the urine was complex and included bands that correspond to full-length protein as well as protein fragments thereof. One might speculate that a high molecular mass complex of ∼90 kDa corresponds to YB-1 protein bound to albumin, given the high affinity of both proteins for each other (data not shown).20 S proteasome-mediated cleavage of YB-1 before glycine 220 has been demonstrated before (46Sorokin A.V. Selyutina A.A. Skabkin M.A. Guryanov S.G. Nazimov I.V. Richard C. Th'ng J. Yau J. Sorensen P.H. Ovchinnikov L.P. Evdokimova V. EMBO J. 2005; 24: 3602-3612Crossref PubMed Scopus (126) Google Scholar). The calculated sizes for the resultant fragments are in line with the observed band mobility (corresponding to 30 kDa) during mesangioproliferative nephritis. It will be furthermore of interest to test whether YB-1 protein fragments act differently on receptor activation.The observation of Notch-3 up-regulation as part of the inflammatory response is especially notable in light of a study providing evidence that Notch-3 receptor signaling profoundly alters intracellular signaling cascades involved in inflammatory responses, namely Jak2 activation and the subsequent STAT3 phosphorylation (47Kamakura S. Oishi K. Yoshimatsu T. Nakafuku M. Masuyama N. Gotoh Y. Nat. Cell Biol. 2004; 6: 547-554Crossref PubMed Scopus (340) Google Scholar). It may, therefore, be speculated that YB-1 secretion and Notch-3 receptor expression/activation may amplify the inflammatory response of MC conferred by the Jak/STAT (signal transducers and activators of transcription) pathway.In sum, the data presented in this report provide evidence for a role of extracellular YB-1 as a ligand for Notch-3. This contributes to our understanding both of the repertoire of conventional and non-conventional ligands for Notch receptors and for the specificity of the individual receptor isoforms. It also highlights possible new roles of Notch and YB-1 in the inflammatory response. Ramifications of Notch-3 activation by YB-1 could be important in other processes such as stem cell maintenance, leukemogenesis, and lymphangiogenesis. The Y-box (YB) 3The abbreviations used are: YBY-boxEGFepidermal growth factorHEKhuman embryonic kidneyTRITCtetramethylrhodamine isothiocyanateHKhuman kidneyCREBcAMP-response element-binding proteinHAhemagglutininIPimmunoprecipitateICN3Notch-3 intracellular domainPDGFplatelet-derived growth factorCADASIL syndromecerebral autosomal-dominant arteriopathy with subcortical infarcts and leukencephalopathyGAPDHglyceraldehyde-3-phosphate dehydrogenasePBSphosphate-buffered salineRIPA bufferradioimmune precipitation assay bufferMCmesangial cellsCSLCBP, Suppressor of Hairless, Lag-1CBPCREB-binding protein. 3The abbreviations used are: YBY-boxEGFepidermal growth factorHEKhuman embryonic kidneyTRITCtetramethylrhodamine isothiocyanateHKhuman kidneyCREBcAMP-response element-binding proteinHAhemagglutininIPimmunoprecipitateICN3Notch-3 intracellular domainPDGFplatelet-derived growth factorCADASIL syndromecerebral autosomal-dominant arteriopathy with subcortical infarcts and leukencephalopathyGAPDHglyceraldehyde-3-phosphate dehydrogenasePBSphosphate-buffered salineRIPA bufferradioimmune precipitation assay bufferMCmesangial cellsCSLCBP, Suppressor of Hairless, Lag-1CBPCREB-binding protein. protein-1 belongs to the cold shock family, which is notable for its conservation throughout evolution (1Kohno K. Izumi H. Uchiumi T. Ashizuka M. Kuwano M. BioEssays. 2003; 25: 691-698Crossref PubMed Scopus (431) Google Scholar). Cold shock proteins play pleiotropic roles in gene regulation, pre-mRNA splicing (2Raffetseder U. Frye B. Rauen T. Jürchott K. Royer H.D. Jansen P.L. Mertens P.R. J. Biol. Chem. 2003; 278: 18241-18248Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar), mRNA translocation, mRNA masking, and mRNA translation (3Evdokimova V. Ruzanov P. Anglesio M.S. Sorokin A.V. Ovchinnikov L.P. Buckley J. Triche T.J. Sonenberg N. Sorensen P.H. Mol. Cell. Biol. 2006; 26: 277-292Crossref PubMed Scopus (213) Google Scholar). The prototypic member YB-1 exhibits an exceptional high degree of phylogenetic conservation not only in the cold shock domain but also throughout the rest of the molecule. Y-box epidermal growth factor human embryonic kidney tetramethylrhodamine isothiocyanate human kidney cAMP-response element-binding protein hemagglutinin immunoprecipitate Notch-3 intracellular domain platelet-derived growth factor cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukencephalopathy glyceraldehyde-3-phosphate dehydrogenase phosphate-buffered saline radioimmune precipitation assay buffer mesangial cells CBP, Suppressor of Hairless, Lag-1 CREB-binding protein. Y-box epidermal growth factor human embryonic kidney tetramethylrhodamine isothiocyanate human kidney cAMP-response element-binding protein hemagglutinin immunoprecipitate Notch-3 intracellular domain platelet-derived growth factor cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukencephalopathy glyceraldehyde-3-phosphate dehydrogenase phosphate-buffered saline radioimmune precipitation assay buffer mesangial cells CBP, Suppressor of Hairless, Lag-1 CREB-binding protein. The protein may be divided into three distinct domains, the alanine/glycine/proline-rich N-terminal part, the centrally located cold shock domain, and a C-terminal region characterized by four alternating clusters of basic and acidic amino acids. An interaction with actin has been described for the N-terminal domain (4Ruzanov P.V. Evdokimova V.M. Korneeva N.L. Hershey J.W. Ovchinnikov L.P. J. Cell Sci. 1999; 112: 3487-3496PubMed Google Scholar). The cold shock domain contains basic and aromatic amino acids to attract nucleic acid backbones and to associate with DNA or RNA nucleotide bases. It forms an antiparallel β-barrel, enfolding nucleic acids in a chaperone-like manner (1Kohno K. Izumi H. Uchiumi T. Ashizuka M. Kuwano M. BioEssays. 2003; 25: 691-698Crossref PubMed Scopus (431) Google Scholar). The C-terminal region of YB-1 forms a “charged zipper” with motifs that recognize specific RNA hairpins, contribute to DNA/RNA binding, and function as docking site for other proteins. Recent findings link YB-1 with inflammatory diseases. These include allergic asthma (5Capowski E.E. Esnault S. Bhattacharya S. Malter J.S. J. Immunol. 2001; 167: 5970-5976Crossref PubMed Scopus (82) Google Scholar) and mesangioproliferative nephritis, in which YB-1 is a downstream target of cytokine platelet-derived growth factor (PDGF)-BB (6van Roeyen C.R. Eitner F. Martinkus S. Thieltges S.R. Ostendorf T. Bokemeyer D. Lüscher B. Lüscher-Firzlaff J.M. Floege J. Mertens P.R. J. Am. Soc. Nephrol. 2005; 16: 2985-2996Crossref PubMed Scopus (39) Google Scholar), interferon -γ (7Dooley S. Said H.M. Gressner A.M. Floege J. En-Nia A. Mertens P.R. J. Biol. Chem. 2006; 281: 1784-1795Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar), and granulocyte monocyte-colony stimulating factor (5Capowski E.E. Esnault S. Bhattacharya S. Malter J.S. J. Immunol. 2001; 167: 5970-5976Crossref PubMed Scopus (82) Google Scholar). We demonstrated that YB-1 serves as a transcriptional regulator of RANTES (CCL5) expression in atherosclerosis and renal transplant rejection (8Krohn R. Raffetseder U. Bot I. Zernecke A. Shagdarsuren E. Liehn E.A. van Santbrink P.J. Nelson P.J. Biessen E.A. Mertens P.R. Weber C. Circulation. 2007; 116: 1812-1820Crossref PubMed Scopus (77) Google Scholar, 9Raffetseder U. Rauen T. Djudjaj S. Kretzler M. En-Nia A. Tacke F. Zimmermann H.W. Nelson P.J. Frye B.C. Floege J. Stefanidis I. Weber C. Mertens P.R. Kidney Int. 2009; 75: 185-196Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar). There is emerging evidence that YB-1 is also secreted from mesangial and immune cells via a non-classical secretion pathway (10Frye B.C. Halfter S. Djudjaj S. Muehlenberg P. Weber S. Raffetseder U. En-Nia A. Knott H. Baron J.M. Dooley S. Bernhagen J. Mertens P.R. EMBO Rep. 2009; 10: 783-789Crossref PubMed Scopus (91) Google Scholar). To clarify potential extracellular protein functions, we established a two-hybrid screen with YB-1 as bait and searched for interacting proteins. We identified splicing factor SRp30c (2Raffetseder U. Frye B. Rauen T. Jürchott K. Royer H.D. Jansen P.L. Mertens P.R. J. Biol. Chem. 2003; 278: 18241-18248Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar) and a positive clone encoding for the extracellular EGF domains 13–33 of the receptor Notch-3 as potential partner proteins. Notch-3 belongs to a receptor superfamily encompassing Notch-1 through -4 in vertebrates. Notch signaling imparts cell fate decisions in many tissues, including the immune system (11Maillard I. Fang T. Pear W.S. Annu. Rev. Immunol. 2005; 23: 945-974Crossref PubMed Scopus (373) Google Scholar) and vasculo- and organogenesis in multicellular organisms (12Sestan N. Artavanis-Tsakonas S. Rakic P. Science. 1999; 286: 741-746Crossref PubMed Scopus (494) Google Scholar). Notch receptors constitute single-pass transmembrane proteins that contain repetitive epidermal growth factor-like domain repeats (EGF) and three cysteine-rich Notch/Lin-12 repeats within their extracellular domain. The intracellular domain encompasses seven ankyrin repeats, a nuclear localization signal, tra" @default.
• W2002143651 created "2016-06-24" @default.
• W2002143651 creator A5001704767 @default.
• W2002143651 creator A5002246212 @default.
• W2002143651 creator A5005210369 @default.
• W2002143651 creator A5006492345 @default.
• W2002143651 creator A5033104943 @default.
• W2002143651 creator A5050024715 @default.
• W2002143651 creator A5058204085 @default.
• W2002143651 creator A5059975187 @default.
• W2002143651 creator A5062225576 @default.
• W2002143651 creator A5080194585 @default.
• W2002143651 date "2009-09-01" @default.
• W2002143651 modified "2023-10-14" @default.
• W2002143651 title "YB-1 Acts as a Ligand for Notch-3 Receptors and Modulates Receptor Activation" @default.
• W2002143651 cites W1556322054 @default.
• W2002143651 cites W1642259399 @default.
• W2002143651 cites W1730632510 @default.
• W2002143651 cites W1911156364 @default.
• W2002143651 cites W1964633462 @default.
• W2002143651 cites W1967026151 @default.
• W2002143651 cites W1975771868 @default.
• W2002143651 cites W1977962361 @default.
• W2002143651 cites W1984059331 @default.
• W2002143651 cites W1989955797 @default.
• W2002143651 cites W1995333503 @default.
• W2002143651 cites W2021556801 @default.
• W2002143651 cites W2023603678 @default.
• W2002143651 cites W2024268776 @default.
• W2002143651 cites W2029102082 @default.
• W2002143651 cites W2033369846 @default.
• W2002143651 cites W2036638105 @default.
• W2002143651 cites W2041569598 @default.
• W2002143651 cites W2042344054 @default.
• W2002143651 cites W2043865646 @default.
• W2002143651 cites W2046821312 @default.
• W2002143651 cites W2050635677 @default.
• W2002143651 cites W2053841715 @default.
• W2002143651 cites W2053998044 @default.
• W2002143651 cites W2059330780 @default.
• W2002143651 cites W2059400872 @default.
• W2002143651 cites W2075773133 @default.
• W2002143651 cites W2078767245 @default.
• W2002143651 cites W2084403389 @default.
• W2002143651 cites W2092388342 @default.
• W2002143651 cites W2095959555 @default.
• W2002143651 cites W2099454404 @default.
• W2002143651 cites W2105844486 @default.
• W2002143651 cites W2107318020 @default.
• W2002143651 cites W2116911322 @default.
• W2002143651 cites W2121673648 @default.
• W2002143651 cites W2145111609 @default.
• W2002143651 cites W2152244674 @default.
• W2002143651 cites W2152743343 @default.
• W2002143651 cites W2155233934 @default.
• W2002143651 cites W2162187251 @default.
• W2002143651 cites W2166980528 @default.
• W2002143651 cites W2172022740 @default.
• W2002143651 cites W2187570082 @default.
• W2002143651 cites W2323180929 @default.
• W2002143651 doi "https://doi.org/10.1074/jbc.m109.046599" @default.
• W2002143651 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2785380" @default.
• W2002143651 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19640841" @default.
• W2002143651 hasPublicationYear "2009" @default.
• W2002143651 type Work @default.
• W2002143651 sameAs 2002143651 @default.
• W2002143651 citedByCount "88" @default.
• W2002143651 countsByYear W20021436512012 @default.
• W2002143651 countsByYear W20021436512013 @default.
• W2002143651 countsByYear W20021436512014 @default.
• W2002143651 countsByYear W20021436512015 @default.
• W2002143651 countsByYear W20021436512016 @default.
• W2002143651 countsByYear W20021436512017 @default.
• W2002143651 countsByYear W20021436512018 @default.
• W2002143651 countsByYear W20021436512019 @default.
• W2002143651 countsByYear W20021436512020 @default.
• W2002143651 countsByYear W20021436512021 @default.
• W2002143651 countsByYear W20021436512022 @default.
• W2002143651 countsByYear W20021436512023 @default.
• W2002143651 crossrefType "journal-article" @default.
• W2002143651 hasAuthorship W2002143651A5001704767 @default.
• W2002143651 hasAuthorship W2002143651A5002246212 @default.
• W2002143651 hasAuthorship W2002143651A5005210369 @default.
• W2002143651 hasAuthorship W2002143651A5006492345 @default.
• W2002143651 hasAuthorship W2002143651A5033104943 @default.
• W2002143651 hasAuthorship W2002143651A5050024715 @default.
• W2002143651 hasAuthorship W2002143651A5058204085 @default.
• W2002143651 hasAuthorship W2002143651A5059975187 @default.
• W2002143651 hasAuthorship W2002143651A5062225576 @default.
• W2002143651 hasAuthorship W2002143651A5080194585 @default.
• W2002143651 hasBestOaLocation W20021436511 @default.
• W2002143651 hasConcept C116569031 @default.
• W2002143651 hasConcept C12554922 @default.
• W2002143651 hasConcept C161879069 @default.
• W2002143651 hasConcept C170493617 @default.
• W2002143651 hasConcept C185592680 @default.
• W2002143651 hasConcept C55493867 @default.
• W2002143651 hasConcept C86803240 @default.

• next