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How the TP 53 Family Proteins TP 63 and TP 73 Contribute to Tumorigenesis: Regulators and Effectors
Author(s) -
Candi Eleonora,
Agostini Massimiliano,
Melino Gerry,
Bernassola Francesca
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22523
Subject(s) - biology , effector , transactivation , carcinogenesis , gene isoform , genetics , gene family , protein family , gene , microbiology and biotechnology , computational biology , promoter , transcription factor , gene expression
In mammals, the p53 family comprises two additional members, p63 and p73 (hereafter referred to as TP 53, TP 63, and TP 73, respectively). The usage of two alternative promoters produces protein variants either with (transactivating [ TA ] isoforms) or without (Δ N isoforms) the N ‐terminal transactivation domain ( TAD ). In general, the TA proteins exert TP 53‐like tumor‐suppressive activities through their ability to activate a common set of target genes. The Δ N proteins can act as dominant‐negative inhibitors of the transcriptionally active family members. Additionally, they possess intrinsic‐specific biological activities due to the presence of alternative TAD s, and as a result of engaging a different set of regulators. This review summarizes the current understanding of upstream regulators and downstream effectors of the TP 53 family proteins, with particular emphasis on those that are relevant for their role in tumorigenesis. Furthermore, we highlight the existence of networks and cross‐talks among the TP 53 family members, their modulators, as well as the transcriptional targets.