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Dissection of the functional interaction between p53 and the embryonic proto‐oncoprotein PAX3
Author(s) -
Underwood Timothy J.,
Amin Jay,
Lillycrop Karen A.,
Blaydes Jeremy P.
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.11.056
Subject(s) - transcription factor , regulator , embryonic stem cell , pax3 , microbiology and biotechnology , biology , gene , transcription (linguistics) , cancer research , apoptosis , p53 protein , genetics , linguistics , philosophy
Studies from murine embryogenesis and cancer cells derived from human melanomas have identified a critical role for the transcription factor PAX3 in the suppression of p53 protein accumulation and p53‐dependent apoptosis. Here we show, using a well‐defined over‐expression system, that PAX3 suppresses p53‐dependent transcription from promoters of p53‐responsive genes, notably BAX and HDM2‐P2 , and reduces p53 protein abundance by promoting its degradation. We define the functional domains of PAX3 required for this activity, and furthermore present evidence that PAX3‐dependent inhibition of p53 is independent of binding of the N‐terminal domain of p53 to HDM2, the primary negative regulator of cellular p53 activity.