TY - JOUR
T1 - Interaction of myogenic factors and the retinoblastoma protein mediates muscle cell commitment and differentiation
AU - Gu, Wei
AU - Schneider, Jay W.
AU - Condorelli, Gianluigi
AU - Kaushal, Sunjay
AU - Mahdavi, Vijak
AU - Nadal-Ginard, Bernardo
N1 - Funding Information:
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.
PY - 1993/2/12
Y1 - 1993/2/12
N2 - 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.
AB - 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.
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U2 - 10.1016/0092-8674(93)90110-C
DO - 10.1016/0092-8674(93)90110-C
M3 - Article
C2 - 8381715
AN - SCOPUS:0027499060
SN - 0092-8674
VL - 72
SP - 309
EP - 324
JO - Cell
JF - Cell
IS - 3
ER -