A Study of the Mechanism Underlying the Regulation of TAp63 and Delta Np63 Expressions

The p63 transcription factor is a member of the p53 family. Alternative promoter usage of the p63 gene transcription leads to the production of two major isoforms, the TAp63（with transactivation domain, capable of activating p53 target genes）and 釗Np63（without Nterminal transactivation domain, a dominant negative inhibitor of p53 and p63 functions）. p63 was once considered as a specific marker for keratinocyte stem cell, however, subsequent work by others（including us）showed that the expression pattern of p63 is rather complicated. The relative abundance of TAp63 and 釗Np63 varies with respect to cell differentiation and proliferation. We have shown that in limbal keratinocytes, TAp63 is required for the maintenance of slow cell cycling and undifferentiation, while 釗Np63 is required for rapid cell cycling and proliferation. The observation suggest that p63 plays important roles in the regulation of keratinocyte differentiation and proliferation. In this proposal, we intend to delineate the mechanism underlying the regulation of TAp63 / 釗Np63 expression. We will use human naspharyngeal carcinoma cell and liver cancer cell to study the signaling systems governing the expressions of p63 isoforms and will use limbal epithelial cell to study their roles in the maintainance of the stemness of the limbal epithelial cell. Understanding the regulation of p63 expression should shed light for our understanding of the development, differentiation and maturation of the stratified epithelia. In this proposal, we present some of our preliminary results and propose our future plan along the line of this research work.

Project ID:PC9708-0331
External Project ID:NSC95-2320-B182-029-MY3