Dissection of the functional interaction between p53 and the embryonic proto-oncoprotein PAX3
Dissection of the functional interaction between p53 and the embryonic proto-oncoprotein PAX3
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 reserved
Animals, Genes, Developmental, Humans, Mice, NIH 3T3 Cells, PAX3 Transcription Factor, Paired Box Transcription Factors/chemistry, Protein Binding, Protein Interaction Mapping, Protein Structure, Tertiary, Proto-Oncogene Proteins/chemistry, Proto-Oncogene Proteins c-mdm2, Transcription, Genetic, Tumor Suppressor Protein p53/antagonists & inhibitors
5831-5835
Underwood, Timothy J.
8e81bf60-edd2-4b0e-8324-3068c95ea1c6
Amin, Jay
692a8880-70ff-4b64-a7e9-7d0d53449a30
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Blaydes, Jeremy P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
22 December 2007
Underwood, Timothy J.
8e81bf60-edd2-4b0e-8324-3068c95ea1c6
Amin, Jay
692a8880-70ff-4b64-a7e9-7d0d53449a30
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Blaydes, Jeremy P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
Underwood, Timothy J., Amin, Jay, Lillycrop, Karen A. and Blaydes, Jeremy P.
(2007)
Dissection of the functional interaction between p53 and the embryonic proto-oncoprotein PAX3.
FEBS Letters, 581 (30), .
(doi:10.1016/j.febslet.2007.11.056).
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 reserved
Text
Underwood_FEBS__v2.pdf
- Accepted Manuscript
More information
Published date: 22 December 2007
Keywords:
Animals, Genes, Developmental, Humans, Mice, NIH 3T3 Cells, PAX3 Transcription Factor, Paired Box Transcription Factors/chemistry, Protein Binding, Protein Interaction Mapping, Protein Structure, Tertiary, Proto-Oncogene Proteins/chemistry, Proto-Oncogene Proteins c-mdm2, Transcription, Genetic, Tumor Suppressor Protein p53/antagonists & inhibitors
Identifiers
Local EPrints ID: 62962
URI: http://eprints.soton.ac.uk/id/eprint/62962
ISSN: 0014-5793
PURE UUID: 916d95da-7411-4820-bed5-2480443cfecb
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Date deposited: 11 Sep 2008
Last modified: 24 Apr 2024 01:47
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