Role of p53 family members in the development of Xenopus laevis

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2001-12

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Lu, Pengfei

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Abstract

p53 family members play an essential role in tumor suppression and development. In this report, the developing Xenopus embryos have been used to analyze their role in development by introducing wild-type or dominant negative proteins into early embryos and studying the phenotype with a variety of techniques. Mutant p53 was functionally mapped in order to dissect the possible mechanism underlying its tumorigenic property, which, surprisingly, is independent of the oligomerization domain and does not target its family members. The function of Xenopus p63 was characterized by overexpression of the wild-type protein. Even though it lacks a typical transcriptional activation domain, Xp63 possesses some p53-like activities in controlling the cell cycle and apoptosis. The major sites of Xp63 expression are the epidermis and neural crest, suggesting that it might play a role in the formation of these structures. This is supported by the observation that neural crest formation is affected by overexpression of dominant-negative Xp63. These results suggest that, while sharing many similarities, the p53 family members have distinct functions during early development. Together, these findings have offered a starting point for future study of functional conservation and divergence of these molecules as to their role in cancer and development and have established the Xenopus embryo as an efficacious system for such studies.

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