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Originally published In Press as doi:10.1074/jbc.M411194200 on November 14, 2004

J. Biol. Chem., Vol. 280, Issue 3, 2159-2164, January 21, 2005
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Ectopic Expression of p73{alpha}, but Not p73{beta}, Suppresses Myogenic Differentiation*

Chun-Ying Li, Jiangyu Zhu, and Jean Y. J. Wang{ddagger}

From the Division of Biological Sciences and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093-0322

The TRP73 gene, a member of the p53 family, encodes several variants through differential splicing and use of alternative promoters. At the N terminus, two different promoters generate the full-length and the {Delta}N isoforms, with or without the transactivating domain. At the C terminus, seven isoforms generated through alternative splicing have been cloned. Previous studies have demonstrated that {Delta}N-p73 interferes with p73-induced apoptosis. However, there has been no evidence for functional diversity of the C-terminal p73 variants. In this study, we found that p73{alpha} and p73{beta} exerted differential effect on the differentiation of C2C12 myoblasts. Although p73{beta} lacked any detectable effect on differentiation, p73{alpha} caused a substantial delay in the expression of muscle-specific genes. In co-transfection experiments p73{alpha}, but not p73{beta}, attenuated the transcriptional activity of MyoD. Microarray-based gene profiling confirmed the protraction of MyoD-dependent gene expression in C2C12 cells stably expressing p73{alpha}. Notwithstanding the differential effect on differentiation, p73{alpha} and p73{beta} showed similar activity in sensitizing C2C12 myoblasts to cisplatin-induced cell death. These results demonstrated a functional diversity between the two C-terminal variants of p73 and suggested that p73{alpha} can regulate cellular differentiation in addition to its role in stimulating cell death.


Received for publication, September 30, 2004 , and in revised form, November 1, 2004.

* This work was supported by grants from the National Institutes of Health (to J. Y. J. W). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} To whom correspondence should be addressed. Tel.: 858-534-6253; Fax: 858-822-2002; E-mail: jywang{at}ucsd.edu.


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