The adenovirus E1A oncoprotein recruits the cellular TRRAP/GCN5 histone acetyltransferase complex.
The adenovirus E1A oncoprotein stimulates cell growth and inhibits differentiation by deregulating the normal transcription program via interaction with positive and negative cellular effectors. E1A associates with transcriptional regulatory complexes containing p400 and TRRAP involved in chromatin remodeling and decondensation. TRRAP is a component of three distinct human histone acetyltransferase (HAT) complexes: the TIP60 complex and complexes containing GCN5 or PCAF. We demonstrate here that E1A binds a TRRAP complex that contains the GCN5 acetyltransferase during a normal adenovirus infection. E1A binds GCN5 and TRRAP in vivo early after virus infection. E1A is associated with significant HAT activity in vitro that is partly attributable to GCN5. E1A represses c-Myc- and E2F-1-directed transcriptional activation in vivo by sequestering GCN5 and/or TRRAP. Our results demonstrate that E1A distinctly binds TRRAP/GCN5, p300/CBP and PCAF HAT complexes. Through interactions with multiple HAT complexes, E1A may deregulate cellular transcription programs and facilitate infection by recruiting functional HAT coactivators to viral and cellular promoter regions.
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Steven E
SE
Lang
Patrick
P
Hearing
D048868:Adaptor Proteins, Signal Transducing; D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D017124:Conserved Sequence; D051548:Histone Acetyltransferases; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D048868:Adaptor Proteins, Signal Transducing; D017500:Adenovirus E1A Proteins; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C113829:transformation-transcription domain-associated protein; C501179:KAT2A protein, human