Ectopic expression of p73α, but not p73β, suppresses myogenic differentiation

Abstract

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 ΔN 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 ΔN-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 p73α and p73β exerted differential effect on the differentiation of C2C12 myoblasts. Although p73β lacked any detectable effect on differentiation, p73α caused a substantial delay in the expression of muscle-specific genes. In co-transfection experiments p73α, but not p73β, attenuated the transcriptional activity of MyoD. Microarray-based gene profiling confirmed the protraction of MyoD-dependent gene expression in C2C12 cells stably expressing p73α. Notwithstanding the differential effect on differentiation, p73α and p73β 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 p73α can regulate cellular differentiation in addition to its role in stimulating cell death.