Abstract
The experiments reported here document that the tumor suppressor retinoblastoma protein (pRB) plays an important role in the production and maintenance of the terminally differentiated phenotype of muscle cells. We show that pRB inactivation, through either phosphorylation, binding to T antigen, or genetic alteration, inhibits myogenesis. Moreover, inactivation of pRB in terminally differentiated cells allows them to reenter the cell cycle. In addition to its involvement in the myogenic activities of MyoD, pRB is also required for the cell growth-inhibitory activity of this myogenic factor. We also show that pRB and MyoD directly bind to each other, both in vivo and in vitro, through a region that involves the pocket and the basic-helix-loop-helix domains, respectively. All the results obtained are consistent with the proposal that the effects of MyoD on the cell cycle and of pRB on the myogenic pathway result from the direct binding of the two molecules.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 309-324 |
| Number of pages | 16 |
| Journal | Cell |
| Volume | 72 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 12 1993 |
| Externally published | Yes |
Funding
We thank Drs. W. Kaelin, D. Livingston, H. Weintraub, R. Weinberg, A. D. Miller, K. Peden, E. Harlow, W. E. Wright, J. Pines, T. Hunter, L. Zhu, R. Breitbart, and R. Steinbrich and membersof the Nadal-Ginard laboratory for materials and advice. We also thank Drs. A. Thorburn, J. Feramisco, and A. Lassar for sharing data prior to publication. J. W. S. is supported by a MERCK/American Federation for Clinical Research MD/PhD fellowship. S. K. is a Howard Hughes Medical Institute Medical School Training Fellow. This research has been sup ported in part by grants from the National Institutes of Health and the Muscular Dystrophy Association of America.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
