MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tintignac, L. A. J.
Right arrow Articles by Leibovitch, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tintignac, L. A. J.
Right arrow Articles by Leibovitch, S. A.

 Previous Article

Molecular and Cellular Biology, February 2004, p. 1809-1821, Vol. 24, No. 4
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.4.1809-1821.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mutant MyoD Lacking Cdc2 Phosphorylation Sites Delays M-Phase Entry

Lionel A. J. Tintignac,1 Valentina Sirri,1 Marie Pierre Leibovitch,1 Yann Lécluse,2 Maria Castedo,1 Didier Metivier,1 Guido Kroemer,1 and Serge A. Leibovitch1*

Laboratoire de Génétique Oncologique,1 Service commun de cytofluorometrie, Institut Gustave Roussy, 94805 Villejuif, France2

Received 26 February 2003/ Returned for modification 30 May 2003/ Accepted 15 November 2003

The transcription factors MyoD and Myf-5 control myoblast identity and differentiation. MyoD and Myf-5 manifest opposite cell cycle-specific expression patterns. Here, we provide evidence that MyoD plays a pivotal role at the G2/M transition by controlling the expression of p21Waf1/Cip1 (p21), which is believed to regulate cyclin B-Cdc2 kinase activity in G2. In growing myoblasts, MyoD reaccumulates during G2 concomitantly with p21 before entry into mitosis; MyoD is phosphorylated on Ser5 and Ser200 by cyclin B-Cdc2, resulting in a decrease of its stability and down-regulation of both MyoD and p21. Inducible expression of a nonphosphorylable MyoD A5/A200 enhances the MyoD interaction with the coactivator P/CAF, thereby stimulating the transcriptional activation of a luciferase reporter gene placed under the control of the p21 promoter. MyoD A5/A200 causes sustained p21 expression, which inhibits cyclin B-Cdc2 kinase activity in G2 and delays M-phase entry. This G2 arrest is not observed in p21-/- cells. These results show that in cycling cells MyoD functions as a transcriptional activator of p21 and that MyoD phosphorylation is required for G2/M transition.

* Corresponding author. Mailing address: Laboratoire de Génétique Oncologique, UMR 8125 CNRS, Institut Gustave Roussy, 94805 Villejuif, France. Phone: 01 42 11 45 16. Fax: 01 42 11 52 61. E-mail: leibovit{at}igr.fr.

Molecular and Cellular Biology, February 2004, p. 1809-1821, Vol. 24, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.4.1809-1821.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2004 by the American Society for Microbiology. All rights reserved.