Abstract
The insulin-like growth factors (IGFs) have dramatic and complex effects on the growth of many tissues and have been implicated in both the proliferation and differentiation of skeletal muscle cells. A detailed analysis of gene expression was performed in L6E9 myoblast cultures treated with IGF-I to dissect the early events leading to the stimulation of myogenic differentiation by this growth factor. A time course of transcript accumulation in confluent L6E9 myoblasts treated with defined media containing IGF-I revealed an initial transient decrease in myogenic factors, accompanied by an increase in cell cycle markers and cell proliferation. This pattern was reversed at later time points, when the subsequent activation of myogenic factors resulted in a net increase in structural gene expression and larger myotubes. The data presented here support the hypothesis that IGF-I activates proliferation first, and subsequently stimulates events leading to the expression of muscle-specific genes in myogenic cell cultures.
Full Text
The Full Text of this article is available as a PDF (2.6 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ballard F. J., Read L. C., Francis G. L., Bagley C. J., Wallace J. C. Binding properties and biological potencies of insulin-like growth factors in L6 myoblasts. Biochem J. 1986 Jan 1;233(1):223–230. doi: 10.1042/bj2330223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barres B. A., Schmid R., Sendnter M., Raff M. C. Multiple extracellular signals are required for long-term oligodendrocyte survival. Development. 1993 May;118(1):283–295. doi: 10.1242/dev.118.1.283. [DOI] [PubMed] [Google Scholar]
- Beck F., Samani N. J., Penschow J. D., Thorley B., Tregear G. W., Coghlan J. P. Histochemical localization of IGF-I and -II mRNA in the developing rat embryo. Development. 1987 Sep;101(1):175–184. doi: 10.1242/dev.101.1.175. [DOI] [PubMed] [Google Scholar]
- Bondy C. A., Werner H., Roberts C. T., Jr, LeRoith D. Cellular pattern of insulin-like growth factor-I (IGF-I) and type I IGF receptor gene expression in early organogenesis: comparison with IGF-II gene expression. Mol Endocrinol. 1990 Sep;4(9):1386–1398. doi: 10.1210/mend-4-9-1386. [DOI] [PubMed] [Google Scholar]
- Braun T., Bober E., Buschhausen-Denker G., Kohtz S., Grzeschik K. H., Arnold H. H., Kotz S. Differential expression of myogenic determination genes in muscle cells: possible autoactivation by the Myf gene products. EMBO J. 1989 Dec 1;8(12):3617–3625. doi: 10.1002/j.1460-2075.1989.tb08535.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen Y., Bornfeldt K. E., Arner A., Jennische E., Malmqvist U., Uvelius B., Arnqvist H. J. Increase in insulin-like growth factor I in hypertrophying smooth muscle. Am J Physiol. 1994 Feb;266(2 Pt 1):E224–E229. doi: 10.1152/ajpendo.1994.266.2.E224. [DOI] [PubMed] [Google Scholar]
- Coleman M. E., DeMayo F., Yin K. C., Lee H. M., Geske R., Montgomery C., Schwartz R. J. Myogenic vector expression of insulin-like growth factor I stimulates muscle cell differentiation and myofiber hypertrophy in transgenic mice. J Biol Chem. 1995 May 19;270(20):12109–12116. doi: 10.1074/jbc.270.20.12109. [DOI] [PubMed] [Google Scholar]
- Czech M. P. Signal transmission by the insulin-like growth factors. Cell. 1989 Oct 20;59(2):235–238. doi: 10.1016/0092-8674(89)90281-x. [DOI] [PubMed] [Google Scholar]
- Davis R. L., Weintraub H., Lassar A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. doi: 10.1016/0092-8674(87)90585-x. [DOI] [PubMed] [Google Scholar]
- Donoghue M., Ernst H., Wentworth B., Nadal-Ginard B., Rosenthal N. A muscle-specific enhancer is located at the 3' end of the myosin light-chain 1/3 gene locus. Genes Dev. 1988 Dec;2(12B):1779–1790. doi: 10.1101/gad.2.12b.1779. [DOI] [PubMed] [Google Scholar]
- Edmondson D. G., Olson E. N. A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program. Genes Dev. 1989 May;3(5):628–640. doi: 10.1101/gad.3.5.628. [DOI] [PubMed] [Google Scholar]
- Edmondson S. R., Werther G. A., Russell A., LeRoith D., Roberts C. T., Jr, Beck F. Localization of growth hormone receptor/binding protein messenger ribonucleic acid (mRNA) during rat fetal development: relationship to insulin-like growth factor-I mRNA. Endocrinology. 1995 Oct;136(10):4602–4609. doi: 10.1210/endo.136.10.7664680. [DOI] [PubMed] [Google Scholar]
- Edwall D., Schalling M., Jennische E., Norstedt G. Induction of insulin-like growth factor I messenger ribonucleic acid during regeneration of rat skeletal muscle. Endocrinology. 1989 Feb;124(2):820–825. doi: 10.1210/endo-124-2-820. [DOI] [PubMed] [Google Scholar]
- Ewton D. Z., Falen S. L., Florini J. R. The type II insulin-like growth factor (IGF) receptor has low affinity for IGF-I analogs: pleiotypic actions of IGFs on myoblasts are apparently mediated by the type I receptor. Endocrinology. 1987 Jan;120(1):115–123. doi: 10.1210/endo-120-1-115. [DOI] [PubMed] [Google Scholar]
- Ewton D. Z., Florini J. R. Effects of the somatomedins and insulin on myoblast differentiation in vitro. Dev Biol. 1981 Aug;86(1):31–39. doi: 10.1016/0012-1606(81)90312-2. [DOI] [PubMed] [Google Scholar]
- Ewton D. Z., Roof S. L., Magri K. A., McWade F. J., Florini J. R. IGF-II is more active than IGF-I in stimulating L6A1 myogenesis: greater mitogenic actions of IGF-I delay differentiation. J Cell Physiol. 1994 Nov;161(2):277–284. doi: 10.1002/jcp.1041610212. [DOI] [PubMed] [Google Scholar]
- Florini J. R., Ewton D. Z., Evinger-Hodges M. J., Falen S. L., Lau R. L., Regan J. F., Vertel B. M. Stimulation and inhibition of myoblast differentiation by hormones. In Vitro. 1984 Dec;20(12):942–958. doi: 10.1007/BF02619668. [DOI] [PubMed] [Google Scholar]
- Florini J. R., Ewton D. Z., Falen S. L., Van Wyk J. J. Biphasic concentration dependency of stimulation of myoblast differentiation by somatomedins. Am J Physiol. 1986 May;250(5 Pt 1):C771–C778. doi: 10.1152/ajpcell.1986.250.5.C771. [DOI] [PubMed] [Google Scholar]
- Florini J. R., Ewton D. Z. Highly specific inhibition of IGF-I-stimulated differentiation by an antisense oligodeoxyribonucleotide to myogenin mRNA. No effects on other actions of IGF-T. J Biol Chem. 1990 Aug 15;265(23):13435–13437. [PubMed] [Google Scholar]
- Florini J. R., Ewton D. Z., Magri K. A. Hormones, growth factors, and myogenic differentiation. Annu Rev Physiol. 1991;53:201–216. doi: 10.1146/annurev.ph.53.030191.001221. [DOI] [PubMed] [Google Scholar]
- Florini J. R., Ewton D. Z., Roof S. L. Insulin-like growth factor-I stimulates terminal myogenic differentiation by induction of myogenin gene expression. Mol Endocrinol. 1991 May;5(5):718–724. doi: 10.1210/mend-5-5-718. [DOI] [PubMed] [Google Scholar]
- Florini J. R., Magri K. A., Ewton D. Z., James P. L., Grindstaff K., Rotwein P. S. "Spontaneous" differentiation of skeletal myoblasts is dependent upon autocrine secretion of insulin-like growth factor-II. J Biol Chem. 1991 Aug 25;266(24):15917–15923. [PubMed] [Google Scholar]
- Furlanetto R. W., Harwell S. E., Frick K. K. Insulin-like growth factor-I induces cyclin-D1 expression in MG63 human osteosarcoma cells in vitro. Mol Endocrinol. 1994 Apr;8(4):510–517. doi: 10.1210/mend.8.4.8052269. [DOI] [PubMed] [Google Scholar]
- Füchtbauer E. M., Westphal H. MyoD and myogenin are coexpressed in regenerating skeletal muscle of the mouse. Dev Dyn. 1992 Jan;193(1):34–39. doi: 10.1002/aja.1001930106. [DOI] [PubMed] [Google Scholar]
- Garfinkel L. I., Periasamy M., Nadal-Ginard B. Cloning and characterization of cDNA sequences corresponding to myosin light chains 1, 2, and 3, troponin-C, troponin-T, alpha-tropomyosin, and alpha-actin. J Biol Chem. 1982 Sep 25;257(18):11078–11086. [PubMed] [Google Scholar]
- Gu Y., Turck C. W., Morgan D. O. Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature. 1993 Dec 16;366(6456):707–710. doi: 10.1038/366707a0. [DOI] [PubMed] [Google Scholar]
- Guo K., Wang J., Andrés V., Smith R. C., Walsh K. MyoD-induced expression of p21 inhibits cyclin-dependent kinase activity upon myocyte terminal differentiation. Mol Cell Biol. 1995 Jul;15(7):3823–3829. doi: 10.1128/mcb.15.7.3823. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halevy O., Novitch B. G., Spicer D. B., Skapek S. X., Rhee J., Hannon G. J., Beach D., Lassar A. B. Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD. Science. 1995 Feb 17;267(5200):1018–1021. doi: 10.1126/science.7863327. [DOI] [PubMed] [Google Scholar]
- Han V. K., D'Ercole A. J., Lund P. K. Cellular localization of somatomedin (insulin-like growth factor) messenger RNA in the human fetus. Science. 1987 Apr 10;236(4798):193–197. doi: 10.1126/science.3563497. [DOI] [PubMed] [Google Scholar]
- Han V. K., Hill D. J., Strain A. J., Towle A. C., Lauder J. M., Underwood L. E., D'Ercole A. J. Identification of somatomedin/insulin-like growth factor immunoreactive cells in the human fetus. Pediatr Res. 1987 Sep;22(3):245–249. doi: 10.1203/00006450-198709000-00001. [DOI] [PubMed] [Google Scholar]
- Harper J. W., Adami G. R., Wei N., Keyomarsi K., Elledge S. J. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993 Nov 19;75(4):805–816. doi: 10.1016/0092-8674(93)90499-g. [DOI] [PubMed] [Google Scholar]
- Harrington E. A., Bennett M. R., Fanidi A., Evan G. I. c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO J. 1994 Jul 15;13(14):3286–3295. doi: 10.1002/j.1460-2075.1994.tb06630.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ito H., Hiroe M., Hirata Y., Tsujino M., Adachi S., Shichiri M., Koike A., Nogami A., Marumo F. Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes. Circulation. 1993 May;87(5):1715–1721. doi: 10.1161/01.cir.87.5.1715. [DOI] [PubMed] [Google Scholar]
- Jahn L., Sadoshima J., Izumo S. Cyclins and cyclin-dependent kinases are differentially regulated during terminal differentiation of C2C12 muscle cells. Exp Cell Res. 1994 Jun;212(2):297–307. doi: 10.1006/excr.1994.1147. [DOI] [PubMed] [Google Scholar]
- Jennische E., Hansson H. A. Regenerating skeletal muscle cells express insulin-like growth factor I. Acta Physiol Scand. 1987 Jun;130(2):327–332. doi: 10.1111/j.1748-1716.1987.tb08144.x. [DOI] [PubMed] [Google Scholar]
- Jennische E., Olivecrona H. Transient expression of insulin-like growth factor I immunoreactivity in skeletal muscle cells during postnatal development in the rat. Acta Physiol Scand. 1987 Dec;131(4):619–622. doi: 10.1111/j.1748-1716.1987.tb08283.x. [DOI] [PubMed] [Google Scholar]
- Jennische E., Skottner A., Hansson H. A. Satellite cells express the trophic factor IGF-I in regenerating skeletal muscle. Acta Physiol Scand. 1987 Jan;129(1):9–15. doi: 10.1111/j.1748-1716.1987.tb08034.x. [DOI] [PubMed] [Google Scholar]
- Kiess M., Gill R. M., Hamel P. A. Expression of the positive regulator of cell cycle progression, cyclin D3, is induced during differentiation of myoblasts into quiescent myotubes. Oncogene. 1995 Jan 5;10(1):159–166. [PubMed] [Google Scholar]
- Lassar A. B., Skapek S. X., Novitch B. Regulatory mechanisms that coordinate skeletal muscle differentiation and cell cycle withdrawal. Curr Opin Cell Biol. 1994 Dec;6(6):788–794. doi: 10.1016/0955-0674(94)90046-9. [DOI] [PubMed] [Google Scholar]
- Lipton B. H., Schultz E. Developmental fate of skeletal muscle satellite cells. Science. 1979 Sep 21;205(4412):1292–1294. doi: 10.1126/science.472747. [DOI] [PubMed] [Google Scholar]
- Liu J. P., Baker J., Perkins A. S., Robertson E. J., Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell. 1993 Oct 8;75(1):59–72. [PubMed] [Google Scholar]
- MAURO A. Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol. 1961 Feb;9:493–495. doi: 10.1083/jcb.9.2.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mangiacapra F. J., Roof S. L., Ewton D. Z., Florini J. R. Paradoxical decrease in myf-5 messenger RNA levels during induction of myogenic differentiation by insulin-like growth factors. Mol Endocrinol. 1992 Dec;6(12):2038–2044. doi: 10.1210/mend.6.12.1337140. [DOI] [PubMed] [Google Scholar]
- Matsushime H., Roussel M. F., Ashmun R. A., Sherr C. J. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle. Cell. 1991 May 17;65(4):701–713. doi: 10.1016/0092-8674(91)90101-4. [DOI] [PubMed] [Google Scholar]
- McClearn D., Medville R., Noden D. Muscle cell death during the development of head and neck muscles in the chick embryo. Dev Dyn. 1995 Apr;202(4):365–377. doi: 10.1002/aja.1002020406. [DOI] [PubMed] [Google Scholar]
- Medford R. M., Nguyen H. T., Nadal-Ginard B. Transcriptional and cell cycle-mediated regulation of myosin heavy chain gene expression during muscle cell differentiation. J Biol Chem. 1983 Sep 25;258(18):11063–11073. [PubMed] [Google Scholar]
- Nadal-Ginard B. Commitment, fusion and biochemical differentiation of a myogenic cell line in the absence of DNA synthesis. Cell. 1978 Nov;15(3):855–864. doi: 10.1016/0092-8674(78)90270-2. [DOI] [PubMed] [Google Scholar]
- Pajak L., Mariappan M., Wieczorek D. F. Reprogramming of myosin light chain 1/3 expression in muscle heterokaryons. Dev Biol. 1991 May;145(1):28–39. doi: 10.1016/0012-1606(91)90210-t. [DOI] [PubMed] [Google Scholar]
- Pardee A. B. G1 events and regulation of cell proliferation. Science. 1989 Nov 3;246(4930):603–608. doi: 10.1126/science.2683075. [DOI] [PubMed] [Google Scholar]
- Parker S. B., Eichele G., Zhang P., Rawls A., Sands A. T., Bradley A., Olson E. N., Harper J. W., Elledge S. J. p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells. Science. 1995 Feb 17;267(5200):1024–1027. doi: 10.1126/science.7863329. [DOI] [PubMed] [Google Scholar]
- Periasamy M., Strehler E. E., Garfinkel L. I., Gubits R. M., Ruiz-Opazo N., Nadal-Ginard B. Fast skeletal muscle myosin light chains 1 and 3 are produced from a single gene by a combined process of differential RNA transcription and splicing. J Biol Chem. 1984 Nov 10;259(21):13595–13604. [PubMed] [Google Scholar]
- Quinn L. S., Roh J. S. Overexpression of the human type-1 insulin-like growth factor receptor in rat L6 myoblasts induces ligand-dependent cell proliferation and inhibition of differentiation. Exp Cell Res. 1993 Oct;208(2):504–508. doi: 10.1006/excr.1993.1273. [DOI] [PubMed] [Google Scholar]
- Rao S. S., Chu C., Kohtz D. S. Ectopic expression of cyclin D1 prevents activation of gene transcription by myogenic basic helix-loop-helix regulators. Mol Cell Biol. 1994 Aug;14(8):5259–5267. doi: 10.1128/mcb.14.8.5259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rao S. S., Kohtz D. S. Positive and negative regulation of D-type cyclin expression in skeletal myoblasts by basic fibroblast growth factor and transforming growth factor beta. A role for cyclin D1 in control of myoblast differentiation. J Biol Chem. 1995 Feb 24;270(8):4093–4100. doi: 10.1074/jbc.270.8.4093. [DOI] [PubMed] [Google Scholar]
- Rhodes S. J., Konieczny S. F. Identification of MRF4: a new member of the muscle regulatory factor gene family. Genes Dev. 1989 Dec;3(12B):2050–2061. doi: 10.1101/gad.3.12b.2050. [DOI] [PubMed] [Google Scholar]
- Roeder R. A., Hossner K. L., Sasser R. G., Gunn J. M. Regulation of protein turnover by recombinant human insulin-like growth factor-I in L6 myotube cultures. Horm Metab Res. 1988 Nov;20(11):698–700. doi: 10.1055/s-2007-1010920. [DOI] [PubMed] [Google Scholar]
- Rosen K. M., Wentworth B. M., Rosenthal N., Villa-Komaroff L. Specific, temporally regulated expression of the insulin-like growth factor II gene during muscle cell differentiation. Endocrinology. 1993 Aug;133(2):474–481. doi: 10.1210/endo.133.2.8393762. [DOI] [PubMed] [Google Scholar]
- Rosenthal N., Berglund E. B., Wentworth B. M., Donoghue M., Winter B., Bober E., Braun T., Arnold H. H. A highly conserved enhancer downstream of the human MLC1/3 locus is a target for multiple myogenic determination factors. Nucleic Acids Res. 1990 Nov 11;18(21):6239–6246. doi: 10.1093/nar/18.21.6239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenthal N. Identification of regulatory elements of cloned genes with functional assays. Methods Enzymol. 1987;152:704–720. doi: 10.1016/0076-6879(87)52075-4. [DOI] [PubMed] [Google Scholar]
- Rosenthal N., Kornhauser J. M., Donoghue M., Rosen K. M., Merlie J. P. Myosin light chain enhancer activates muscle-specific, developmentally regulated gene expression in transgenic mice. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7780–7784. doi: 10.1073/pnas.86.20.7780. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenthal S. M., Cheng Z. Q. Opposing early and late effects of insulin-like growth factor I on differentiation and the cell cycle regulatory retinoblastoma protein in skeletal myoblasts. Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10307–10311. doi: 10.1073/pnas.92.22.10307. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schneider J. W., Gu W., Zhu L., Mahdavi V., Nadal-Ginard B. Reversal of terminal differentiation mediated by p107 in Rb-/- muscle cells. Science. 1994 Jun 3;264(5164):1467–1471. doi: 10.1126/science.8197461. [DOI] [PubMed] [Google Scholar]
- Sherr C. J. G1 phase progression: cycling on cue. Cell. 1994 Nov 18;79(4):551–555. doi: 10.1016/0092-8674(94)90540-1. [DOI] [PubMed] [Google Scholar]
- Sicinski P., Donaher J. L., Parker S. B., Li T., Fazeli A., Gardner H., Haslam S. Z., Bronson R. T., Elledge S. J., Weinberg R. A. Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell. 1995 Aug 25;82(4):621–630. doi: 10.1016/0092-8674(95)90034-9. [DOI] [PubMed] [Google Scholar]
- Skapek S. X., Rhee J., Spicer D. B., Lassar A. B. Inhibition of myogenic differentiation in proliferating myoblasts by cyclin D1-dependent kinase. Science. 1995 Feb 17;267(5200):1022–1024. doi: 10.1126/science.7863328. [DOI] [PubMed] [Google Scholar]
- Smith J., Fowkes G., Schofield P. N. Programmed cell death in dystrophic (mdx) muscle is inhibited by IGF-II. Cell Death Differ. 1995 Oct;2(4):243–251. [PubMed] [Google Scholar]
- Strehler E. E., Periasamy M., Strehler-Page M. A., Nadal-Ginard B. Myosin light-chain 1 and 3 gene has two structurally distinct and differentially regulated promoters evolving at different rates. Mol Cell Biol. 1985 Nov;5(11):3168–3182. doi: 10.1128/mcb.5.11.3168. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sussenbach J. S. The gene structure of the insulin-like growth factor family. Prog Growth Factor Res. 1989;1(1):33–48. doi: 10.1016/0955-2235(89)90040-9. [DOI] [PubMed] [Google Scholar]
- Tollefsen S. E., Lajara R., McCusker R. H., Clemmons D. R., Rotwein P. Insulin-like growth factors (IGF) in muscle development. Expression of IGF-I, the IGF-I receptor, and an IGF binding protein during myoblast differentiation. J Biol Chem. 1989 Aug 15;264(23):13810–13817. [PubMed] [Google Scholar]
- Tollefsen S. E., Sadow J. L., Rotwein P. Coordinate expression of insulin-like growth factor II and its receptor during muscle differentiation. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1543–1547. doi: 10.1073/pnas.86.5.1543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Turo K. A., Florini J. R. Hormonal stimulation of myoblast differentiation in the absence of DNA synthesis. Am J Physiol. 1982 Nov;243(5):C278–C284. doi: 10.1152/ajpcell.1982.243.5.C278. [DOI] [PubMed] [Google Scholar]
- Vandenburgh H. H., Karlisch P., Shansky J., Feldstein R. Insulin and IGF-I induce pronounced hypertrophy of skeletal myofibers in tissue culture. Am J Physiol. 1991 Mar;260(3 Pt 1):C475–C484. doi: 10.1152/ajpcell.1991.260.3.C475. [DOI] [PubMed] [Google Scholar]
- Wang J., Nadal-Ginard B. Regulation of cyclins and p34CDC2 expression during terminal differentiation of C2C12 myocytes. Biochem Biophys Res Commun. 1995 Jan 5;206(1):82–88. doi: 10.1006/bbrc.1995.1012. [DOI] [PubMed] [Google Scholar]
- Wentworth B. M., Donoghue M., Engert J. C., Berglund E. B., Rosenthal N. Paired MyoD-binding sites regulate myosin light chain gene expression. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1242–1246. doi: 10.1073/pnas.88.4.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winston J. T., Pledger W. J. Growth factor regulation of cyclin D1 mRNA expression through protein synthesis-dependent and -independent mechanisms. Mol Biol Cell. 1993 Nov;4(11):1133–1144. doi: 10.1091/mbc.4.11.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Won K. A., Xiong Y., Beach D., Gilman M. Z. Growth-regulated expression of D-type cyclin genes in human diploid fibroblasts. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9910–9914. doi: 10.1073/pnas.89.20.9910. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wright W. E., Sassoon D. A., Lin V. K. Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD. Cell. 1989 Feb 24;56(4):607–617. doi: 10.1016/0092-8674(89)90583-7. [DOI] [PubMed] [Google Scholar]
- Xiong Y., Hannon G. J., Zhang H., Casso D., Kobayashi R., Beach D. p21 is a universal inhibitor of cyclin kinases. Nature. 1993 Dec 16;366(6456):701–704. doi: 10.1038/366701a0. [DOI] [PubMed] [Google Scholar]
- Yaffe D. Retention of differentiation potentialities during prolonged cultivation of myogenic cells. Proc Natl Acad Sci U S A. 1968 Oct;61(2):477–483. doi: 10.1073/pnas.61.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]