Open AccessAdenovirus E1A targets p400 to induce the cellular oncoprotein Myc
Author(s) -
Kathryn A Tworkowski,
Abhishek A. Chakraborty,
Andrew V. Samuelson,
Yvette R. Seger,
Masako Narita,
Gregory J. Han,
Scott W. Lowe,
William P. Tansey
Publication year - 2008
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0802095105
Subject(s) - transcription factor , proto oncogene proteins c myc , carcinogenesis , microbiology and biotechnology , mutant , cancer research , biology , gene , transcription (linguistics) , genetics , linguistics , philosophy
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.
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