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  • Original Paper
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MyoD induces apoptosis in the absence of RB function through a p21WAF1-dependent re-localization of cyclin/cdk complexes to the nucleus

Oncogene volume 21, pages 8114–8127 (2002)Cite this article

A Corrigendum to this article was published on 18 March 2003

This article has been updated

Abstract

During differentiation of skeletal myoblasts, MyoD promotes growth arrest through the induction of the cdk inhibitor p21 and the accumulation of hypophosphorylated RB protein. Myoblasts lacking RB function fail to accomplish full differentiation and undergo apoptosis. Here we show that exogenous MyoD induces apoptosis in several cell backgrounds sharing RB inactivation. This process is associated with increased levels of cell cycle-driving proteins and aberrant cell cycle progression. The inability of MyoD to induce apoptosis in a p21-null background, highlights a requirement of p21 in RB-regulated apoptosis during myogenesis. This pro-apoptotic function of p21 cannot be exerted by simple p21 over-expression, but requires the co-operation of MyoD. We also suggest 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. These results establish a novel link between MyoD, p21 and RB during myogenesis, providing new insights into the antagonism between muscle differentiation and loss of RB function.

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Acknowledgements

We gratefully acknowledge Prof Paolo Amati and Dr Vanesa Gottifredi for helpful advice and critical reading of the manuscript. We also thank Drs B Amati, M Caruso and M Crescenzi who made available plasmids and cell lines (see Materials and methods). This work was supported by grants from Associazione Italiana Ricerche sul Cancro (AIRC) and Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR). This paper is dedicated to the memory of our colleague Franco Tató.

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  1. Angelo Peschiaroli

    Present address: Department of Pathology, MSB 548 New York University School of Medicine, 550 First Ave., New York, 10016, NY, USA

Authors and Affiliations

  1. Dipartimento di Biotecnologie Cellulari ed Ematologia, Istituto Pasteur-Fondazione Cenci Bolognetti, Sezione di Genetica Molecolare, Università di Roma La Sapienza, Viale Regina Elena 324, Roma, 00161, Italy

    Angelo Peschiaroli, Rocco Figliola, Luana Coltella, Alessandra Strom & Rossella Maione

  2. Istituto di Tecnologie Biomediche, CNR, V.le Marx 43, Roma, 00137, Italy

    Alessandra Valentini & Igea D'Agnano

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  1. Angelo Peschiaroli
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Correspondence to Rossella Maione.

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Peschiaroli, A., Figliola, R., Coltella, L. et al. MyoD induces apoptosis in the absence of RB function through a p21WAF1-dependent re-localization of cyclin/cdk complexes to the nucleus. Oncogene 21, 8114–8127 (2002). https://doi.org/10.1038/sj.onc.1206010

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