Journal
EXPERIMENTAL CELL RESEARCH
Volume 259, Issue 1, Pages 300-307Publisher
ELSEVIER INC
DOI: 10.1006/excr.2000.4973
Keywords
cyclin E-Cdk2; degradation; G1 phase; MyoD; phosphorylation; ubiquitination
Categories
Ask authors/readers for more resources
Proliferating myoblasts already express MyoD before the induction of differentiation. Overexpression of MyoD in normal and transformed cell lines was shown to block cells from entering S phase, suggesting that the MyoD growth suppressive effect must be tightly controlled in growing myoblasts, Here we show that during G1 phase, but not in G2, MyoD abundance is down-regulated by the ubiquitin-proteasome pathway through phosphorylation of serine 200. Roscovitine, a specific inhibitor of cyclin-Cdk2 complexes, prevents both phosphorylation and degradation of MyoD in G1. Inhibition of the ubiquitin-dependent proteasome pathway by MG132 results in stabilization of MyoD-wt, with little effect on a MyoD mutant where serine 200 is replaced by an alanine. Our results show that MyoD Ser200 is the substrate for phosphorylation by cyclin E-Cdk2 stimulating its degradation by the ubiquitin-proteasome system which controls MyoD levels in G1. Phosphorylation/degradation of MyoD at the end of G1 thus represents the regulatory checkpoint in growing myoblasts allowing progression into S phase in a manner similar to the recently examplified cdk2-phosphorylation/degradation Of p27(Kip1). (C) 2000 Academic Press.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available