Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc

Tworkowski, K. A., Chakraborty, A. A., Samuelson, A. V., Seger, Y. R., Narita, M., Hannon, G. J., Lowe, S. W., Tansey, W. P. (April 2008) Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc. Proc Natl Acad Sci U S A, 105 (16). pp. 6103-6108.

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URL: http://www.ncbi.nlm.nih.gov/pubmed/18413597
DOI: 10.1073/pnas.0802095105

Abstract

Adenovirus E1A drives oncogenesis by targeting key regulatory pathways that are critical for cellular growth control. The interaction of E1A with p400 is essential for many E1A activities, but the downstream target of this interaction is unknown. Here, we present evidence that the oncoprotein transcription factor Myc is the target of this interaction. We show that E1A stabilizes Myc protein via p400 and promotes the coassociation of Myc and p400 at Myc target genes, leading to their transcriptional induction. We also show that E1A requires Myc for its ability to activate Myc-dependent gene expression and induce apoptosis, and that forced expression of Myc is sufficient to rescue the activity of an E1A-mutant defective in p400 binding. Together, these findings establish that Myc, via p400, is an essential downstream target of E1A.

Item Type: Paper
Uncontrolled Keywords: proteolysis transcription transformation apoptosis
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > Myc
organism description > virus > adeno associated virus
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
organism description > virus
CSHL Authors:
Communities: CSHL labs > Hannon lab
CSHL labs > Lowe lab
CSHL labs > Tansey lab
Depositing User: Matt Covey
Date: 22 April 2008
Date Deposited: 28 Feb 2013 16:46
Last Modified: 08 Nov 2017 21:44
PMCID: PMC2329713
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27487

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