MyoD induced cell cycle arrest is associated with increased nuclear affinity of the Rb protein

AM Thorburn, PA Walton and JR Feramisco

Cancer Center, University of California, San Diego, La Jolla 92093-0636.

In studying the mechanism through which the myogenic determination protein MyoD prevents entry into the S phase of the cell cycle, we have found a relationship between MyoD and the retinoblastoma (Rb) tumor suppressor protein. By direct needle microinjection of purified recombinant MyoD protein into quiescent fibroblasts, which were then induced to proliferate by serum, we found that MyoD arrested progression of the cell cycle, in agreement with studies utilizing expression constructs for MyoD. By studying temporal changes in cells injected with MyoD protein, it was found that MyoD did not prevent serum induced expression of the protooncogene c-Fos, an event that occurs in the G0 to G1 transition of the cycle. Injection of the MyoD protein as late as 8 h after the addition of serum still caused an inhibition in DNA synthesis, suggesting that MyoD inhibits the G1 to S transition as opposed to the G0 to G1 transition. MyoD injection did not prevent the expression of cyclin A. However MyoD injection did result in a block in the increase in Rb extractibility normally seen in late G1 phase cells. As this phenomenon is associated with the hyperphosphorylation of Rb at this point in the cell cycle and is correlated with progression into S phase, this provides further evidence that MyoD blocks the cycle late in G1.

Volume 4, Issue 7, pp. 705-713, 07/01/1993
Copyright © 1993 by The American Society for Cell Biology

This article has been cited by other articles:

				F. De Santa, S. Albini, E. Mezzaroma, L. Baron, A. Felsani, and M. Caruso pRb-Dependent Cyclin D3 Protein Stabilization Is Required for Myogenic Differentiation Mol. Cell. Biol., October 15, 2007; 27(20): 7248 - 7265. [Abstract] [Full Text] [PDF]

				I. Mariappan and V. K. Parnaik Sequestration of pRb by Cyclin D3 Causes Intranuclear Reorganization of Lamin A/C during Muscle Cell Differentiation Mol. Biol. Cell, April 1, 2005; 16(4): 1948 - 1960. [Abstract] [Full Text] [PDF]

				C. S. Guo, C. Degnin, T. A. Fiddler, D. Stauffer, and M. J. Thayer Regulation of MyoD Activity and Muscle Cell Differentiation by MDM2, pRb, and Sp1 J. Biol. Chem., June 13, 2003; 278(25): 22615 - 22622. [Abstract] [Full Text] [PDF]

				A. Mal, D. Chattopadhyay, M. K. Ghosh, R. Y.C. Poon, T. Hunter, and M. L. Harter p21 and Retinoblastoma Protein Control the Absence of DNA Replication in Terminally Differentiated Muscle Cells J. Cell Biol., April 17, 2000; 149(2): 281 - 292. [Abstract] [Full Text] [PDF]

				C. Cenciarelli, F. De Santa, P. L. Puri, E. Mattei, L. Ricci, F. Bucci, A. Felsani, and M. Caruso Critical Role Played by Cyclin D3 in the MyoD-Mediated Arrest of Cell Cycle during Myoblast Differentiation Mol. Cell. Biol., July 1, 1999; 19(7): 5203 - 5217. [Abstract] [Full Text] [PDF]

				M. Kitzmann, G. Carnac, M. Vandromme, M. Primig, N. J.C. Lamb, and A. Fernandez The Muscle Regulatory Factors MyoD and Myf-5 Undergo Distinct Cell Cycle-specific Expression in Muscle Cells J. Cell Biol., September 21, 1998; 142(6): 1447 - 1459. [Abstract] [Full Text] [PDF]

				A. Song, Q. Wang, M. G. Goebl, and M. A. Harrington Phosphorylation of Nuclear MyoD Is Required for Its Rapid Degradation Mol. Cell. Biol., September 1, 1998; 18(9): 4994 - 4999. [Abstract] [Full Text]

				C J Sherr and J M Roberts Inhibitors of mammalian G1 cyclin-dependent kinases. Genes & Dev., May 15, 1995; 9(10): 1149 - 1163. [PDF]

				O Halevy, B. Novitch, D. Spicer, S. Skapek, J Rhee, G. Hannon, D Beach, and A. Lassar Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD Science, February 17, 1995; 267(5200): 1018 - 1021. [Abstract] [PDF]

				S. Skapek, J Rhee, D. Spicer, and A. Lassar Inhibition of myogenic differentiation in proliferating myoblasts by cyclin D1-dependent kinase Science, February 17, 1995; 267(5200): 1022 - 1024. [Abstract] [PDF]

				S. Parker, G Eichele, P Zhang, A Rawls, A. Sands, A Bradley, E. Olson, J. Harper, and S. Elledge p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells Science, February 17, 1995; 267(5200): 1024 - 1027. [Abstract] [PDF]

				V. Petkova, M. J. Romanowski, I. Sulijoadikusumo, D. Rohne, P. Kang, T. Shenk, and A. Usheva Interaction between YY1 and the Retinoblastoma Protein. REGULATION OF CELL CYCLE PROGRESSION IN DIFFERENTIATED CELLS J. Biol. Chem., March 9, 2001; 276(11): 7932 - 7936. [Abstract] [Full Text] [PDF]