Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc.
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.
Tworkowski
Kathryn A
KA
Cold Spring Harbor Laboratory, and Howard Hughes Medical Institute, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Chakraborty
Abhishek A
AA
Samuelson
Andrew V
AV
Seger
Yvette R
YR
Narita
Masako
M
Hannon
Gregory J
GJ
Lowe
Scott W
SW
Tansey
William P
WP
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002472:Cell Transformation, Viral; D047369:Chromatin Immunoprecipitation; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D004265:DNA Helicases; C498558:EP400 protein, human