TP53 family members and human cancers

Jean Bénard, Setha Douc-Rasy, Jean Charles Ahomadegbe

    Résultats de recherche: Contribution à un journalArticle 'review'Revue par des pairs

    196 Citations (Scopus)

    Résumé

    Based on gene sequence homologies, a p53 (TP53) gene family become apparent with the addition of the most recently identified p63 (TP73L; formerly TP63) and p73 (TP73) genes to the already known p53. The p53 gene encodes for a unique protein eliciting well-known tumor suppressor gene (TSG) properties that mediate cellular response to DNA damage, e.g., cell cycle arrest or apoptosis. In contrast, both homologues specify an array of isoforms different in their N- and C-terminal domains. Transactivating isoforms, such as TAp63/p73, show TSG properties similar to p53, while isoforms lacking N-terminal transactivating domain such as ΔNp63/p73, induce a functional block against p53 as well as TAp63/p73 activities. Both p63/p73 types of isoforms are involved in development: p63 is critical for epithelial stem cell renewal and epithelial homeostasis, and p73 is involved in neurogenesis and natural immune response. These facts support interdependent functions for the p53 family members, which appear linked together in a complex and tight regulation network to fulfill cellular functions related to DNA damage and tissue homeostasis maintenance. The lack of p63/p73 mutations in human cancers rule out a typical TSG role for either of the p53 homologues. Nonetheless, p63 and p73 genes seem strongly involved in malignancy acquisition and maintenance process because of: 1) their tissue identities, and 2) their close interplay activities within the p53 family members, and primarily through the negative regulatory role played by ΔNp63/p73 isoforms for cell death control and differentiation.

    langue originaleAnglais
    Pages (de - à)182-191
    Nombre de pages10
    journalHuman Mutation
    Volume21
    Numéro de publication3
    Les DOIs
    étatPublié - 18 mars 2003

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