Interaction of myogenic factors and the retinoblastoma protein mediates muscle cell commitment and differentiation

@article{Gu1993InteractionOM,
  title={Interaction of myogenic factors and the retinoblastoma protein mediates muscle cell commitment and differentiation},
  author={Wei Gu and Jay W. Schneider and Gianluigi Condorelli and Sunjay Kaushal and Vijak Mahdavi and Bernardo Nadal-Ginard},
  journal={Cell},
  year={1993},
  volume={72},
  pages={309-324}
}
The Role of the Retinoblastoma Protein Family in Skeletal Myogenesis
TLDR
It is shown that in the absence of Rb, differentiating primary myoblasts fused to form short myotubes that never twitched and degenerated via a non-apoptotic mechanism, demonstrating that pRb is required to inhibit apoptosis in myoblast and autophagy in myot tubes but not to activate the differentiation program.
MyoD induced cell cycle arrest is associated with increased nuclear affinity of the Rb protein.
TLDR
It was found that direct needle microinjection of purified recombinant MyoD protein into quiescent fibroblasts, which were then induced to proliferate by serum, found that MyiD arrested progression of the cell cycle, in agreement with studies utilizing expression constructs for Myo D.
Regulation of Differentiation by HBP1, a Target of the Retinoblastoma Protein
TLDR
It is reported that the expression of HBP1 unexpectedly blocked muscle cell differentiation without interfering with cell cycle exit and proposed a model in which a checkpoint of positive and negative regulation may coordinate cell cycleexit with MyoD family activation to give fidelity and progression in differentiation.
p21 and p57 control muscle differentiation at the myogenin step
TLDR
It is shown that two Cdk inhibitors, p21 and p57, redundantly control differentiation of skeletal muscle and alveoli in the lungs and indicate a role for cell-cycle exit in myogenin function.
Disruption of the MyoD/p21 Pathway in Rhabdomyosarcoma
TLDR
Although p21 is wild type in RMS, there is an inverse correlation between the levels of p21 and MyoD in these tumors, suggesting that the pathway which would lead to G1 arrest from endogenous p21 activity is defective.
Crosstalk between cell cycle regulators and the myogenic factor MyoD in skeletal myoblasts
TLDR
Accurate synchronization of dividing myoblasts revealed that MyoD and Myf5 are themselves subject to specific cell cycle-dependent regulation, with myoD at its highest level in early G1 and its lowest level at the G1 to S phase transition.
Rb functions to inhibit apoptosis during myocyte differentiation.
TLDR
It is demonstrated that Rb functions downstream from the Cdk inhibitors to coordinate cell cycle withdrawal with programmed cell death during myocyte differentiation.
The activity of differentiation factors induces apoptosis in polyomavirus large T-expressing myoblasts.
TLDR
It is reported that myoblasts expressing wild-type PyLT, when subjected to differentiation stimuli, undergo cell death and that this cell death can be defined as apoptosis.
MyoD induces apoptosis in the absence of RB function through a p21WAF1-dependent re-localization of cyclin/cdk complexes to the nucleus
TLDR
It is shown that exogenous MyoD induces apoptosis in several cell backgrounds sharing RB inactivation, and it is suggested that the essential aspect of p21 activity involved in such a process is related to its ability to induce the nuclear accumulation and aberrant activity of cyclin/cdk complexes.
The molecular regulation of myogenesis
TLDR
A functional role for MyoD during satellite cell activation and muscle repair has been identified in vivo, which cannot be substituted for by the other MRFs, putting forward the hypothesis that these factors also play specific biological roles following muscle injury and repair.
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References

SHOWING 1-10 OF 95 REFERENCES
MyoD induces growth arrest independent of differentiation in normal and transformed cells.
TLDR
It is concluded that MyoD is a prototypic gene capable of functionally activating intracellular growth inhibitory pathways and seems to occur by means of a parallel pathway to the one that leads to myogenesis.
Cell proliferation inhibited by MyoD1 independently of myogenic differentiation
CELL growth and differentiation are usually mutually exclusive1. Transformation of myoblasts by retroviruses containing the myc oncogene inhibits differentiation, preventing cells from withdrawing
Aberrant regulation of MyoD1 contributes to the partially defective myogenic phenotype of BC3H1 cells [published erratum appears in J Cell Biol 1990 Jun;110(6):2231]
TLDR
It is reported that expression of an exogenous MyoD1 cDNA in BC3H1 cells was sufficient to elevate the expression of alpha-cardiac actin and fast myosin light chain, and to convert these cells to a phenotype that forms multinucleate myotubes during differentiation.
The retinoblastoma protein physically associates with the human cdc2 kinase
TLDR
Results suggest that this kinase identified as the cell cycle-regulating kinase p34cdc2 or a closely related enzyme is one of the major regulators of pRB.
Expression and state of phosphorylation of the retinoblastoma susceptibility gene product in cycling and noncycling human hematopoietic cells.
TLDR
There are lineage-specific differences in both the regulation of Rb phosphorylation and RB1 gene expression in lymphoid and myeloid cells, linked to the ability of a cell to synthesize DNA.
Fos and Jun repress transcriptional activation by myogenin and MyoD: the amino terminus of Jun can mediate repression.
TLDR
It is shown that the growth factor-inducible proto-oncogenes c-fos, c-jun, and junB mimic the effects of exogenous growth factors and suppress trans-activation of the muscle creatine kinase enhancer by myogenin and MyoD and that members of the Jun family can be distinguished on the basis of their effects on muscle-specific transcription.
Adenovirus E1A products suppress myogenic differentiation and inhibit transcription from muscle-specific promoters
TLDR
The results support the hypothesis that the suppression of differentiation by ElA products is effected by an ElA-mediated block in the transcriptional activation of cellular genes by specific developmentally regulated cis-acting promoter elements.
MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts.
TLDR
Exposure of a complementary DNA (cDNA) encoding the mouse MyoD1 protein in a variety of fibroblast and adipoblast cell lines converts them to myogenic cells and expression of only 68 amino acids of Myo D1 is sufficient to activate myogenesis in stably transfected 10T1/2 cells.
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