FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2034001658> ?p ?o ?g. }

• W2034001658 endingPage "141" @default.
• W2034001658 startingPage "131" @default.
• W2034001658 abstract "The ultimate stem cell, the oocyte, is frequently very large. For example, Drosophila and Xenopus oocytes are ∼105 times larger than normal somatic cells. Importantly, once the large oocytes are fertilized, the resulting embryonic cells proliferate rapidly. Moreover, these divisions occur in the absence of cell growth and are not governed by normal cell cycle controls. Observations suggest that mitogens and cell growth signals modulate proliferation by upregulating G1-phase cyclins, which in turn promote cell division. Like embryonic cells, the proliferation of cancer cells is largely independent of mitogens and growth factors. This occurs, in part, because many proteins that are known to modulate G1-phase cyclin activity are frequently mutated in cancer cells. Interestingly, we have found that both the expression and the activity of G1-phase cyclins is modulated by growth rate and cell size in yeast. These and other data suggest that proliferative capacity correlates with cell size. Thus, a major goal of our laboratory is to use yeast to investigate the relationship between proliferation rate, G1-phase cyclins, growth rate, and cell size. The elucidation of this relationship will help clarify the role of cell size in promoting proliferation in both normal and cancer cells. The ultimate stem cell, the oocyte, is frequently very large. For example, Drosophila and Xenopus oocytes are ∼105 times larger than normal somatic cells. Importantly, once the large oocytes are fertilized, the resulting embryonic cells proliferate rapidly. Moreover, these divisions occur in the absence of cell growth and are not governed by normal cell cycle controls. Observations suggest that mitogens and cell growth signals modulate proliferation by upregulating G1-phase cyclins, which in turn promote cell division. Like embryonic cells, the proliferation of cancer cells is largely independent of mitogens and growth factors. This occurs, in part, because many proteins that are known to modulate G1-phase cyclin activity are frequently mutated in cancer cells. Interestingly, we have found that both the expression and the activity of G1-phase cyclins is modulated by growth rate and cell size in yeast. These and other data suggest that proliferative capacity correlates with cell size. Thus, a major goal of our laboratory is to use yeast to investigate the relationship between proliferation rate, G1-phase cyclins, growth rate, and cell size. The elucidation of this relationship will help clarify the role of cell size in promoting proliferation in both normal and cancer cells. The most obvious differences between different animals are differences in cell size, but for some reason the zoologists have paid singularly little attention to them. J. B. S. Haldane, On Being the Right Size 1927 Size is a fundamental and useful descriptive quality of all organisms. Remarkably, organisms display an almost incomprehensible range of sizes. For example, the largest organism, the Blue Whale, is over 19 billion times larger than the smallest single cell plankton. Comparing the largest and smallest multicellular organisms still reveals an amazing spectrum of size. The smallest marine rotifer has less than 100 cells as compared with the nearly 100 quadrillion cells of a Blue Whale. Given the amazing diversity of organism size, it is striking that cells themselves are quite uniform in size. Most animal cells are 10–20 μm in diameter and rarely vary more than 2-fold outside of this size range (Tessier, 1939Tessier G. Biometrie de la cellule.Tabulae Biol. 1939; 19: 1-64Google Scholar;Altman and Katz, 1961Altman P.L. Katz D.D. Blood and Other Body Fluids. Washington, Federation of American Societies for Experimental Biology1961Google Scholar;Alberts et al., 1994Alberts B. Bray D. Lewis J. Raff M. Watson J.D. Molecular Biology of the Cell. New York, Garland1994Google Scholar;Conlon and Raff, 1999Conlon I. Raff M. Size control in animal development.Cell. 1999; 96: 235-244Abstract Full Text Full Text PDF PubMed Scopus (585) Google Scholar). The relative constancy of cell size within diverse organisms suggests that the mechanism of cell size regulation is conserved. But despite these observations, very little is known about the biological mechanisms that control the size of cells or organisms. The remarkable homogeneity of cell size observed in populations of cells is achieved by coordination of cell growth with division. This occurs because external stimuli, such as nutrients, growth factors, and mitogens, stimulate cell growth and division equivalently. Although often used inter-changeably, it is important to stress that cell growth is not synonymous with proliferation. Proliferation refers to increases in cell numbers whereas growth refers to increases in cell mass (discussed inSu and O'Farrell, 1998Su T.T. O'Farrell P.H. Size control: Cell proliferation does not equal growth.Curr Biol. 1998; 8: R687-R689Abstract Full Text Full Text PDF PubMed Google Scholar;Conlon and Raff, 1999Conlon I. Raff M. Size control in animal development.Cell. 1999; 96: 235-244Abstract Full Text Full Text PDF PubMed Scopus (585) Google Scholar). Recently, the mechanisms that control the regulation of cell size and act to coordinate cell growth with proliferation have become an area of intense research (reviewed inJorgensen and Tyers, 2004Jorgensen P. Tyers M. How cells coordinate growth and division.Curr Biol. 2004; 14: R1014-R1027Abstract Full Text Full Text PDF PubMed Scopus (411) Google Scholar). Prior to the 1950s research on cell size control was virtually non-existent. But a Pub-Med literature search reveals that in the past 5 y there has been an average of nearly 300 “cell size” manuscripts per year as compared with an average of less than two per year 40 y ago Figure 1. This trend is likely to continue as more and more important insights are being made into the genetic, biochemical, and molecular mechanisms that ensure cell size homeostasis (reviewed inJorgensen and Tyers, 2004Jorgensen P. Tyers M. How cells coordinate growth and division.Curr Biol. 2004; 14: R1014-R1027Abstract Full Text Full Text PDF PubMed Scopus (411) Google Scholar). Several decades ago, Hartwell and coworkers achieved the first insight into the mechanisms that coordinate cell growth with proliferation (Hartwell et al., 1970Hartwell L.H. Culotti J. Reid B. Genetic control of the cell-division cycle in yeast. I. Detection of mutants.Proc Natl Acad Sci USA. 1970; 66: 352-359Crossref PubMed Scopus (354) Google Scholar,Hartwell et al., 1974Hartwell L.H. Culotti J. Pringle J.R. Reid B.J. Genetic control of the cell division cycle in yeast.Science. 1974; 183: 46-51Crossref PubMed Scopus (704) Google Scholar;Hartwell, 1974Hartwell L.H. Saccharomyces cerevisiae cell cycle.Bacteriol Rev. 1974; 38: 164-198Crossref PubMed Google Scholar;Hartwell and Unger, 1977Hartwell L.H. Unger M.W. Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division.J Cell Biol. 1977; 75: 422-435Crossref PubMed Scopus (358) Google Scholar). By analyzing temperature-sensitive mutants in the yeast Saccharomyces cerevisiae, they found that the inactivation of some genes essential for proliferation resulted in cells that arrested in specific phases of the cell cycle. Because these mutants blocked progression through the cell division cycle (cdc mutants), the genes encoding these mutants were called CDC genes (Hartwell et al., 1970Hartwell L.H. Culotti J. Reid B. Genetic control of the cell-division cycle in yeast. I. Detection of mutants.Proc Natl Acad Sci USA. 1970; 66: 352-359Crossref PubMed Scopus (354) Google Scholar,Hartwell et al., 1974Hartwell L.H. Culotti J. Pringle J.R. Reid B.J. Genetic control of the cell division cycle in yeast.Science. 1974; 183: 46-51Crossref PubMed Scopus (704) Google Scholar;Hartwell, 1974Hartwell L.H. Saccharomyces cerevisiae cell cycle.Bacteriol Rev. 1974; 38: 164-198Crossref PubMed Google Scholar;Hartwell and Unger, 1977Hartwell L.H. Unger M.W. Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division.J Cell Biol. 1977; 75: 422-435Crossref PubMed Scopus (358) Google Scholar). Analysis of the function of CDC genes has greatly elucidated the genetic and biochemical pathways that control cell cycle progression (Hartwell et al., 1970Hartwell L.H. Culotti J. Reid B. Genetic control of the cell-division cycle in yeast. I. Detection of mutants.Proc Natl Acad Sci USA. 1970; 66: 352-359Crossref PubMed Scopus (354) Google Scholar,Hartwell et al., 1974Hartwell L.H. Culotti J. Pringle J.R. Reid B.J. Genetic control of the cell division cycle in yeast.Science. 1974; 183: 46-51Crossref PubMed Scopus (704) Google Scholar;Hartwell et al., 1974Hartwell L.H. Culotti J. Pringle J.R. Reid B.J. Genetic control of the cell division cycle in yeast.Science. 1974; 183: 46-51Crossref PubMed Scopus (704) Google Scholar;Hartwell, 1974Hartwell L.H. Saccharomyces cerevisiae cell cycle.Bacteriol Rev. 1974; 38: 164-198Crossref PubMed Google Scholar;Hartwell and Unger, 1977Hartwell L.H. Unger M.W. Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division.J Cell Biol. 1977; 75: 422-435Crossref PubMed Scopus (358) Google Scholar). Today, more than 50 CDC genes have been identified (Murray and Hunt, 1993Murray A. Hunt The Cell Cycle. Oxford, University Press1993Google Scholar). Most of these have been cloned and nearly all have human homologues (Murray and Hunt, 1993Murray A. Hunt The Cell Cycle. Oxford, University Press1993Google Scholar). Although all cdc mutants result in specific cell cycle arrests, the largest group consisting of 22 cdc mutants, arrest in G1 phase (Murray and Hunt, 1993Murray A. Hunt The Cell Cycle. Oxford, University Press1993Google Scholar). Careful analysis of these mutants revealed three fundamental details of the basic architecture of the cell cycle. First, it was discovered that the cell cycle is composed of a series of inter-dependent steps that are initiated at the transition point between G1 and S phase. Because of the relationship between this transition and cell cycle progression, this point was named Start in yeast Figure 2 (Hartwell et al., 1970Hartwell L.H. Culotti J. Reid B. Genetic control of the cell-division cycle in yeast. I. Detection of mutants.Proc Natl Acad Sci USA. 1970; 66: 352-359Crossref PubMed Scopus (354) Google Scholar,Hartwell et al., 1974Hartwell L.H. Culotti J. Pringle J.R. Reid B.J. Genetic control of the cell division cycle in yeast.Science. 1974; 183: 46-51Crossref PubMed Scopus (704) Google Scholar;Hartwell, 1974Hartwell L.H. Saccharomyces cerevisiae cell cycle.Bacteriol Rev. 1974; 38: 164-198Crossref PubMed Google Scholar;Hartwell and Unger, 1977Hartwell L.H. Unger M.W. Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division.J Cell Biol. 1977; 75: 422-435Crossref PubMed Scopus (358) Google Scholar). Subsequently, it was shown that Start is analogous to the “restriction point” in mammalian cells (Pardee, 1974Pardee A.B. A restriction point for control of normal animal cell proliferation.Proc Natl Acad Sci USA. 1974; 71: 1286-1290Crossref PubMed Scopus (1022) Google Scholar;Zetterberg et al., 1995Zetterberg A. Larsson O. Wiman K.G. What is the restriction point?.Curr Opin Cell Biol. 1995; 7: 835-842Crossref PubMed Scopus (280) Google Scholar;Blagosklonny and Pardee, 2002Blagosklonny M.V. Pardee A.B. The restriction point of the cell cycle.Cell Cycle. 2002; 1: 103-110Crossref PubMed Scopus (71) Google Scholar) Figure 2. The archetype G1-phase CDC gene, CDC28, encodes a cyclin-dependent kinase that is required for progression past Start (reviewed inReed et al., 1991Reed S.I. Wittenberg C. Lew D.J. Dulic V. Henze M. G1 control in yeast and animal cells.Cold Spring Harb Symp Quant Biol. 1991; 56: 61-67Crossref PubMed Google Scholar;Reed, 1992Reed S.I. The role of p34 kinases in the G1 to S-phase transition.Annu Rev Cell Biol. 1992; 8: 529-561Crossref PubMed Scopus (265) Google Scholar;Nasmyth, 1993Nasmyth K. Control of the yeast cell cycle by the Cdc28 protein kinase.Curr Opin Cell Biol. 1993; 5: 166-179Crossref PubMed Scopus (404) Google Scholar;Cross, 1995Cross F.R. Starting the cell cycle: What's the point?.Curr Opin Cell Biol. 1995; 7: 790-797Crossref PubMed Scopus (102) Google Scholar;Futcher, 1996Futcher B. Cyclins and the wiring of the yeast cell cycle.Yeast. 1996; 12: 1635-1646Crossref PubMed Scopus (92) Google Scholar;Mendenhall and Hodge, 1998Mendenhall M.D. Hodge A.E. Regulation of Cdc28 cyclin-dependent protein kinase activity during the cell cycle of the yeast Saccharomyces cerevisiae.Microbiol Mol Biol Rev. 1998; 62: 1191-1243Crossref PubMed Google Scholar). Importantly, CDC28 is highly conserved, and a homologue, CDC2, has been identified in all higher eukaryotes that have been examined (reviewed inReed et al., 1991Reed S.I. Wittenberg C. Lew D.J. Dulic V. Henze M. G1 control in yeast and animal cells.Cold Spring Harb Symp Quant Biol. 1991; 56: 61-67Crossref PubMed Google Scholar;Reed, 1992Reed S.I. The role of p34 kinases in the G1 to S-phase transition.Annu Rev Cell Biol. 1992; 8: 529-561Crossref PubMed Scopus (265) Google Scholar;Nasmyth, 1993Nasmyth K. Control of the yeast cell cycle by the Cdc28 protein kinase.Curr Opin Cell Biol. 1993; 5: 166-179Crossref PubMed Scopus (404) Google Scholar;Cross, 1995Cross F.R. Starting the cell cycle: What's the point?.Curr Opin Cell Biol. 1995; 7: 790-797Crossref PubMed Scopus (102) Google Scholar;Futcher, 1996Futcher B. Cyclins and the wiring of the yeast cell cycle.Yeast. 1996; 12: 1635-1646Crossref PubMed Scopus (92) Google Scholar;Mendenhall and Hodge, 1998Mendenhall M.D. Hodge A.E. Regulation of Cdc28 cyclin-dependent protein kinase activity during the cell cycle of the yeast Saccharomyces cerevisiae.Microbiol Mol Biol Rev. 1998; 62: 1191-1243Crossref PubMed Google Scholar). Like CDC28, CDC2 is required for progression past the “restriction point.” Second, it was found that progression past Start is dependent upon cell growth and the attainment of a minimum cell size (Hartwell and Unger, 1977Hartwell L.H. Unger M.W. Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division.J Cell Biol. 1977; 75: 422-435Crossref PubMed Scopus (358) Google Scholar;Johnston et al., 1977Johnston G.C. Pringle J.R. Hartwell L.H. Coordination of growth with cell division in the yeast Saccharomyces cerevisiae.Exp Cell Res. 1977; 105: 79-98Crossref PubMed Scopus (535) Google Scholar;Carter and Jagadish, 1978Carter B.L. Jagadish M.N. The relationship between cell size and cell division in the yeast Saccharomyces cerevisiae.Exp Cell Res. 1978; 112: 15-24Crossref PubMed Scopus (43) Google Scholar;Johnston et al., 1979Johnston G.C. Ehrhardt C.W. Lorincz A. Carter B.L. Regulation of cell size in the yeast Saccharomyces cerevisiae.J Bacteriol. 1979; 137: 1-5Crossref PubMed Google Scholar;Lorincz and Coulter, 1979Lorincz A. Coulter Bi-A Control of cell size at bud initiation in Saccharomyces cerevisiae.J Gen Micro. 1979; 113: 287-295Crossref Scopus (48) Google Scholar;Alberts et al., 1994Alberts B. Bray D. Lewis J. Raff M. Watson J.D. Molecular Biology of the Cell. New York, Garland1994Google Scholar) Figure 2. A subset of G1-phase cdc mutants blocks cell growth. In this manner, cells smaller than the required minimum cell size arrest before Start (Hartwell and Unger, 1977Hartwell L.H. Unger M.W. Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division.J Cell Biol. 1977; 75: 422-435Crossref PubMed Scopus (358) Google Scholar;Johnston et al., 1977Johnston G.C. Pringle J.R. Hartwell L.H. Coordination of growth with cell division in the yeast Saccharomyces cerevisiae.Exp Cell Res. 1977; 105: 79-98Crossref PubMed Scopus (535) Google Scholar,Johnston et al., 1979Johnston G.C. Ehrhardt C.W. Lorincz A. Carter B.L. Regulation of cell size in the yeast Saccharomyces cerevisiae.J Bacteriol. 1979; 137: 1-5Crossref PubMed Google Scholar;Carter and Jagadish, 1978Carter B.L. Jagadish M.N. The relationship between cell size and cell division in the yeast Saccharomyces cerevisiae.Exp Cell Res. 1978; 112: 15-24Crossref PubMed Scopus (43) Google Scholar;Lorincz and Coulter, 1979Lorincz A. Coulter Bi-A Control of cell size at bud initiation in Saccharomyces cerevisiae.J Gen Micro. 1979; 113: 287-295Crossref Scopus (48) Google Scholar;Alberts et al., 1994Alberts B. Bray D. Lewis J. Raff M. Watson J.D. Molecular Biology of the Cell. New York, Garland1994Google Scholar). To date, little is known about the biochemical mechanisms responsible for linking cell growth and cell size to proliferation. Third, although it was shown that proliferation was dependent upon cell growth, it was found that the converse is not true. Most cdc mutants that arrest cells in G1 phase continue to grow in mass at near normal rates (Hartwell and Unger, 1977Hartwell L.H. Unger M.W. Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division.J Cell Biol. 1977; 75: 422-435Crossref PubMed Scopus (358) Google Scholar;Johnston et al., 1977Johnston G.C. Pringle J.R. Hartwell L.H. Coordination of growth with cell division in the yeast Saccharomyces cerevisiae.Exp Cell Res. 1977; 105: 79-98Crossref PubMed Scopus (535) Google Scholar,Johnston et al., 1979Johnston G.C. Ehrhardt C.W. Lorincz A. Carter B.L. Regulation of cell size in the yeast Saccharomyces cerevisiae.J Bacteriol. 1979; 137: 1-5Crossref PubMed Google Scholar;Carter and Jagadish, 1978Carter B.L. Jagadish M.N. The relationship between cell size and cell division in the yeast Saccharomyces cerevisiae.Exp Cell Res. 1978; 112: 15-24Crossref PubMed Scopus (43) Google Scholar;Lorincz and Coulter, 1979Lorincz A. Coulter Bi-A Control of cell size at bud initiation in Saccharomyces cerevisiae.J Gen Micro. 1979; 113: 287-295Crossref Scopus (48) Google Scholar;Alberts et al., 1994Alberts B. Bray D. Lewis J. Raff M. Watson J.D. Molecular Biology of the Cell. New York, Garland1994Google Scholar). The manner in which these cdc mutants prevent proliferation despite normal cell growth is not well understood. Thus, a major aim of the cell cycle field is the dissection of the molecular mechanism that links cell growth with proliferation. The genetic study of mutations that disrupt normal cell size control in yeast has been extremely useful in elucidating the mechanisms that coordinate cell growth with proliferation (reviewed inJorgensen and Tyers, 2004Jorgensen P. Tyers M. How cells coordinate growth and division.Curr Biol. 2004; 14: R1014-R1027Abstract Full Text Full Text PDF PubMed Scopus (411) Google Scholar). In the 1980s, yeast geneticists identified the first such cell size mutant, whi1 (Sudbery et al., 1980Sudbery P.E. Goodey A.R. Carter B.L. Genes which control cell proliferation in the yeast Saccharomyces cerevisiae.Nature. 1980; 288: 401-404Crossref PubMed Scopus (128) Google Scholar). The whi1 mutant promoted premature proliferation resulting in a phenotype of abnormally small cells (Sudbery et al., 1980Sudbery P.E. Goodey A.R. Carter B.L. Genes which control cell proliferation in the yeast Saccharomyces cerevisiae.Nature. 1980; 288: 401-404Crossref PubMed Scopus (128) Google Scholar;Cross, 1988Cross F.R. DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae.Mol Cell Biol. 1988; 8: 4675-4684Crossref PubMed Scopus (310) Google Scholar;Nash et al., 1988Nash R. Tokiwa G. Anand S. Erickson K. Futcher A.B. The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog.EMBO J. 1988; 7: 4335-4346Crossref PubMed Scopus (375) Google Scholar). The cloning and analysis of this gene revealed that it encoded a truncated and stabilized G1-phase cyclin, Cln3, that upregulates the activity of the Cdc28 (Sudbery et al., 1980Sudbery P.E. Goodey A.R. Carter B.L. Genes which control cell proliferation in the yeast Saccharomyces cerevisiae.Nature. 1980; 288: 401-404Crossref PubMed Scopus (128) Google Scholar;Cross, 1988Cross F.R. DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae.Mol Cell Biol. 1988; 8: 4675-4684Crossref PubMed Scopus (310) Google Scholar;Nash et al., 1988Nash R. Tokiwa G. Anand S. Erickson K. Futcher A.B. The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog.EMBO J. 1988; 7: 4335-4346Crossref PubMed Scopus (375) Google Scholar). Subsequently, it has been demonstrated that Clns are rate-limiting for progression past Start (Dirick et al., 1995Dirick L. Bohm T. Nasmyth K. Roles and regulation of Cln–Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae.EMBO J. 1995; 14: 4803-4813Crossref PubMed Scopus (274) Google Scholar;Schneider et al., 2004Schneider B.L. Zhang J. Markwardt J. Tokiwa G. Volpe T. Honey S. Futcher B. Growth rate and cell size modulate the synthesis of, and requirement for, G1-phase cyclins at start.Mol Cell Biol. 2004; 24: 10802-10813Crossref PubMed Scopus (51) Google Scholar). Furthermore, over-expression of G1-phase cyclins advances proliferation and dramatically reduces cell size (Dirick et al., 1995Dirick L. Bohm T. Nasmyth K. Roles and regulation of Cln–Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae.EMBO J. 1995; 14: 4803-4813Crossref PubMed Scopus (274) Google Scholar;Schneider et al., 2004Schneider B.L. Zhang J. Markwardt J. Tokiwa G. Volpe T. Honey S. Futcher B. Growth rate and cell size modulate the synthesis of, and requirement for, G1-phase cyclins at start.Mol Cell Biol. 2004; 24: 10802-10813Crossref PubMed Scopus (51) Google Scholar). These observations have demonstrated that Cln–Cdc28 is integral to cell size homeostasis. Interestingly, much of what is known about cell size homeostasis in higher eukaryotes has come from studying cells where growth is not coordinated with proliferation Figure 3. Physiologically, this is a relatively rare event. For instance, oocytes, neurons, and adipocytes can grow without dividing leading to very large cells Figure 3b (discussed inConlon and Raff, 1999Conlon I. Raff M. Size control in animal development.Cell. 1999; 96: 235-244Abstract Full Text Full Text PDF PubMed Scopus (585) Google Scholar;Rudra and Warner, 2004Rudra D. Warner J.R. What better measure than ribosome synthesis?.Genes Dev. 2004; 18: 2431-2436Crossref PubMed Scopus (172) Google Scholar). For example, Drosophila and Xenopus oocytes are ∼105 times larger than normal somatic cells. Once the large oocytes are fertilized, the resulting embryonic cells proliferate rapidly. Moreover, these divisions occur in the absence of cell growth and are not governed by normal cell cycle controls Figure 3c. These observations have led to the theory that cell size may modulate the proliferative capacity of cells. Specifically, it has been suggested that commitment to proliferation is dependent upon the attainment of a minimum “critical cell size” (discussed inPolymenis and Schmidt, 1999Polymenis M. Schmidt E.V. Coordination of cell growth with cell division.Curr Opin Genet Dev. 1999; 9: 76-80Crossref PubMed Scopus (110) Google Scholar;Coelho and Leevers, 2000Coelho C.M. Leevers S.J. Do growth and cell division rates determine cell size in multicellular organisms?.J Cell Sci. 2000; 113: 2927-2934PubMed Google Scholar;Stocker and Hafen, 2000Stocker H. Hafen E. Genetic control of cell size.Curr Opin Genet Dev. 2000; 10: 529-535Crossref PubMed Scopus (204) Google Scholar;Potter and Xu, 2001Potter C.J. Xu T. Mechanisms of size control.Curr Opin Genet Dev. 2001; 11: 279-286Crossref PubMed Scopus (120) Google Scholar;Rupes, 2002Rupes I. Checking cell size in yeast.Trends Genet. 2002; 18: 479-485Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar;Saucedo and Edgar, 2002Saucedo L.J. Edgar B.A. Why size matters: Altering cell size.Curr Opin Genet Dev. 2002; 12: 565-571Crossref PubMed Scopus (99) Google Scholar;Conlon and Raff, 2003Conlon I. Raff M. Differences in the way a mammalian cell and yeast cells coordinate cell growth and cell-cycle progression.J Biol. 2003; 2: 1-10Crossref Google Scholar;Mitchison, 2003Mitchison J.M. Growth during the cell cycle.Int Rev Cytol. 2003; 226: 165-258Crossref PubMed Scopus (121) Google Scholar;Weitzman, 2003Weitzman J.B. Growing without a size checkpoint.J Biol. 2003; 3: 2-5Crossref PubMed Google Scholar;Cooper, 2004Cooper S. Control and maintenance of mammalian cell size.BMC Cell Biol. 2004; 5: 5-35Crossref PubMed Scopus (32) Google Scholar;Jorgensen and Tyers, 2004Jorgensen P. Tyers M. How cells coordinate growth and division.Curr Biol. 2004; 14: R1014-R1027Abstract Full Text Full Text PDF PubMed Scopus (411) Google Scholar;Schneider et al., 2004Schneider B.L. Zhang J. Markwardt J. Tokiwa G. Volpe T. Honey S. Futcher B. Growth rate and cell size modulate the synthesis of, and requirement for, G1-phase cyclins at start.Mol Cell Biol. 2004; 24: 10802-10813Crossref PubMed Scopus (51) Google Scholar). The “critical cell size” theory is supported by the discovery that large cells can divide faster than they can double their mass (Murray and Hunt, 1993Murray A. Hunt The Cell Cycle. Oxford, University Press1993Google Scholar). It is this phenomenon that allows extremely large oocytes to return to the normal size of somatic cells Figure 3c. Because it is proposed that cells are unable to commit to cell division until a minimum cell size is attained, this mechanism also prevents normal somatic cells from getting continually smaller after each division (Murray and Hunt, 1993Murray A. Hunt The Cell Cycle. Oxford, University Press1993Google Scholar). A number of observations in a variety of different organisms support the “critical cell size” theory (discussed inPolymenis and Schmidt, 1999Polymenis M. Schmidt E.V. Coordination of cell growth with cell division.Curr Opin Genet Dev. 1999; 9: 76-80Crossref PubMed Scopus (110) Google Scholar;Coelho and Leevers, 2000Coelho C.M. Leevers S.J. Do growth and cell division rates determine cell size in multicellular organisms?.J Cell Sci. 2000; 113: 2927-2934PubMed Google Scholar;Stocker and Hafen, 2000Stocker H. Hafen E. Genetic control of cell size.Curr Opin Genet Dev. 2000; 10: 529-535Crossref PubMed Scopus (204) Google Scholar;Potter and Xu, 2001Potter C.J. Xu T. Mechanisms of size control.Curr Opin Genet Dev. 2001; 11: 279-286Crossref PubMed Scopus (120) Google Scholar;Rupes, 2002Rupes I. Checking cell size in yeast.Trends Genet. 2002; 18: 479-485Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar;Saucedo and Edgar, 2002Saucedo L.J. Edgar B.A. Why size matters: Altering cell size.Curr Opin Genet Dev. 2002; 12: 565-571Crossref PubMed Scopus (99) Google Scholar;Conlon and Raff, 2003Conlon I. Raff M. Differences in the way a mammalian cell and yeast cells coordinate cell growth and cell-cycle progression.J Biol. 2003; 2: 1-10Crossref Google Scholar;Mitchison, 2003Mitchison J.M. Growth during the cell cycle.Int Rev Cytol. 2003; 226: 165-258Crossref PubMed Scopus (121) Google Scholar;Weitzman, 2003Weitzman J.B. Growing without a size checkpoint.J Biol. 2003; 3: 2-5Crossref PubMed Google Scholar;Cooper, 2004Cooper S. Control and maintenance of mammalian cell size.BMC Cell Biol. 2004; 5: 5-35Crossref PubMed Scopus (32) Google Scholar;Jorgensen and Tyers, 2004Jorgensen P. Tyers M. How cells coordinate growth and division.Curr Biol. 2004; 14: R1014-R1027Abstract Full Text Full Text PDF PubMed Scopus (411) Google Scholar;Schneider et al., 2004Schneider B.L. Zhang J. Markwardt J. Tokiwa G. Volpe T. Honey S. Futcher B. Growth rate and cell size modulate the synthesis of, and requirement for, G1-phase cyclins at start.Mol Cell Biol. 2004; 24: 10802-10813Crossref PubMed Scopus (51) Google Scholar). But because size is a rather amorphous characteristic, it has proved very difficult to extend these observations from a correlative to causative relationship. Moreover, despite the fact that G1-phase Cdks are integral to both cell size homeostasis and proliferation, the relationship between cell size, G1-phase Cdk activity, and proliferative capacity is not well understood. In addition, whereas cell growth is required for proliferation, it is not known how cell size affects cell growth. Finally, it is unclear how a cell might sense its size or how cell size might trigger cell division. Thus, the two major goals in this field are: (1) To determine if cell size has a causative role in promoting cell division, and (2) To determine the molecular mechanism that links cell growth to proliferative potential. Like embryonic cells, the proliferation of cancer cells is largely independent of mitogens and growth factors. This occurs, in part, because the pathways known to modulate G1-phase cyclin activity are mutated or disrupted in nearly every cancer cell (Kastan and Bartek, 2004Kastan M.B. Bartek J. Cell-cycle checkpoints and cancer.Nature. 2004; 432: 316-323Crossref PubMed Scopus (2030) Google Scholar;Massague, 2004Massague J. G1 cell-cycle control and cancer.Nature. 2004; 432: 298-306Crossref PubMed Scopus (890) Google Scholar;Schneider and Kulesz-Martin, 2004Schneider B.L. Kulesz-Martin M. Destructive cycles: The role of genomic instability and adaptation in carcinogenesis.Carcinogenesis. 2004; 25: 2033-2044Crossref PubMed Scopus (51) Google Scholar). In fact, G1-phase cyclin levels are elevated in a number of cancers (Hunter and Pines, 1991Hunter T. Pines J. Cyclins and cancer.Cell. 1991; 66: 1071-1074Abstract Full Text PDF PubMed Scopus (383) Google Scholar;Steeg and Zhou, 1998Steeg P.S. Zhou Q. Cyclins and breast cancer.Breast Cancer Res Treat. 1998; 52: 17-28Crossref PubMed Sc" @default.
• W2034001658 created "2016-06-24" @default.
• W2034001658 creator A5027057272 @default.
• W2034001658 creator A5057209439 @default.
• W2034001658 creator A5080668672 @default.
• W2034001658 creator A5086907603 @default.
• W2034001658 date "2005-11-01" @default.
• W2034001658 modified "2023-10-16" @default.
• W2034001658 title "The Importance of Being Big" @default.
• W2034001658 cites W144129310 @default.
• W2034001658 cites W1483745657 @default.
• W2034001658 cites W1524554804 @default.
• W2034001658 cites W1547033864 @default.
• W2034001658 cites W1557900165 @default.
• W2034001658 cites W1563500075 @default.
• W2034001658 cites W1569574258 @default.
• W2034001658 cites W1584196254 @default.
• W2034001658 cites W1590458072 @default.
• W2034001658 cites W1656825184 @default.
• W2034001658 cites W169216998 @default.
• W2034001658 cites W1800736106 @default.
• W2034001658 cites W1849061432 @default.
• W2034001658 cites W1909702956 @default.
• W2034001658 cites W1965239527 @default.
• W2034001658 cites W1968883815 @default.
• W2034001658 cites W1971060360 @default.
• W2034001658 cites W1974037176 @default.
• W2034001658 cites W1976811517 @default.
• W2034001658 cites W1981413140 @default.
• W2034001658 cites W1981557521 @default.
• W2034001658 cites W1984264526 @default.
• W2034001658 cites W1986616568 @default.
• W2034001658 cites W1989830594 @default.
• W2034001658 cites W1994523623 @default.
• W2034001658 cites W1995361163 @default.
• W2034001658 cites W1995752504 @default.
• W2034001658 cites W1998738134 @default.
• W2034001658 cites W2006545082 @default.
• W2034001658 cites W2009517747 @default.
• W2034001658 cites W2009837683 @default.
• W2034001658 cites W2015038174 @default.
• W2034001658 cites W2015498847 @default.
• W2034001658 cites W2022429702 @default.
• W2034001658 cites W2026265704 @default.
• W2034001658 cites W2029620430 @default.
• W2034001658 cites W2029922809 @default.
• W2034001658 cites W2030303101 @default.
• W2034001658 cites W2032590819 @default.
• W2034001658 cites W2038638792 @default.
• W2034001658 cites W2042827497 @default.
• W2034001658 cites W2047693210 @default.
• W2034001658 cites W2047746661 @default.
• W2034001658 cites W2048499098 @default.
• W2034001658 cites W2048899019 @default.
• W2034001658 cites W2051960144 @default.
• W2034001658 cites W2053804880 @default.
• W2034001658 cites W2059378726 @default.
• W2034001658 cites W2061523903 @default.
• W2034001658 cites W2064670731 @default.
• W2034001658 cites W2068311060 @default.
• W2034001658 cites W2072659475 @default.
• W2034001658 cites W2073194342 @default.
• W2034001658 cites W2077029264 @default.
• W2034001658 cites W2078477504 @default.
• W2034001658 cites W2078822212 @default.
• W2034001658 cites W2080918762 @default.
• W2034001658 cites W2085495204 @default.
• W2034001658 cites W2088127501 @default.
• W2034001658 cites W2089921110 @default.
• W2034001658 cites W2093330988 @default.
• W2034001658 cites W2131367252 @default.
• W2034001658 cites W2140948740 @default.
• W2034001658 cites W2142884934 @default.
• W2034001658 cites W2146794103 @default.
• W2034001658 cites W2155507858 @default.
• W2034001658 cites W2157758135 @default.
• W2034001658 cites W2158679973 @default.
• W2034001658 cites W2160236189 @default.
• W2034001658 cites W2160256138 @default.
• W2034001658 cites W2160594729 @default.
• W2034001658 cites W2164963113 @default.
• W2034001658 cites W2170486182 @default.
• W2034001658 cites W2172229929 @default.
• W2034001658 cites W2199878503 @default.
• W2034001658 cites W2323738288 @default.
• W2034001658 cites W4211194339 @default.
• W2034001658 cites W4300200228 @default.
• W2034001658 cites W55455380 @default.
• W2034001658 doi "https://doi.org/10.1111/j.1087-0024.2005.200414.x" @default.
• W2034001658 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16358818" @default.
• W2034001658 hasPublicationYear "2005" @default.
• W2034001658 type Work @default.
• W2034001658 sameAs 2034001658 @default.
• W2034001658 citedByCount "3" @default.
• W2034001658 countsByYear W20340016582015 @default.
• W2034001658 countsByYear W20340016582019 @default.
• W2034001658 crossrefType "journal-article" @default.
• W2034001658 hasAuthorship W2034001658A5027057272 @default.

• next