Ectopic expression of p73alpha, but not p73beta, suppresses myogenic differentiation.
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 DeltaN 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 DeltaN-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 p73alpha and p73beta exerted differential effect on the differentiation of C2C12 myoblasts. Although p73beta lacked any detectable effect on differentiation, p73alpha caused a substantial delay in the expression of muscle-specific genes. In co-transfection experiments p73alpha, but not p73beta, attenuated the transcriptional activity of MyoD. Microarray-based gene profiling confirmed the protraction of MyoD-dependent gene expression in C2C12 cells stably expressing p73alpha. Notwithstanding the differential effect on differentiation, p73alpha and p73beta 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 p73alpha can regulate cellular differentiation in addition to its role in stimulating cell death.
Li
Chun-Ying
CY
Division of Biological Sciences and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093-0322, USA.
Zhu
Jiangyu
J
Wang
Jean Y J
JY
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D016147:Genes, Tumor Suppressor; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D012326:RNA Splicing; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins