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Dissection of the functional interaction between p53 and the embryonic proto-oncoprotein PAX3

By Timothy J. Underwood, Jay Amin, Karen A. Lillycrop and Jeremy P. Blaydes

Abstract

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 de. ne 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. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserve

Topics: RC0254, QH426
Year: 2007
OAI identifier: oai:eprints.soton.ac.uk:62962
Provided by: e-Prints Soton

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