title: Adenovirus E1A requires the yeast SAGA histone acetyltransferase complex and associates with SAGA components Gcn5 and Tra1.
abstract: The budding yeast Saccharomyces cerevisiae was used as a model system to study the function of the adenovirus E1A oncoprotein. Previously we demonstrated that expression of the N-terminal 82 amino acids of E1A in yeast causes pronounced growth inhibition and specifically interferes with SWI/SNF-dependent transcriptional activation. Further genetic analysis identified the yeast transcription factor Adr1 as a high copy suppressor of E1A function. Transcriptional activation by Adr1 requires interaction with co-activator proteins Ada2 and Gcn5, components of histone acetyltransferase complexes including ADA and SAGA. Analysis of mutant alleles revealed that several components of the SAGA complex, including proteins from the Ada, Spt, and Taf classes were required for E1A-induced growth inhibition. Growth inhibition also depended on the Gcn5 histone acetyltransferase, and point mutations within the Gcn5 HAT domain rendered cells E1A-resistant. Also required was SAGA component Tra1, a homologue of the mammalian TRRAP protein which is required for c-myc and E1A induced cellular transformation. Additionally, Gcn5 protein could associate with E1A in vitro in a manner that depended on the N-terminal domain of E1A, and Tra1 protein was co-immunoprecipitated with E1A in vivo. These results indicate a strong requirement for intact SAGA complex for E1A to function in yeast, and suggest a role for SAGA-like complexes in mammalian cell transformation.
authors.affiliation: Department of Microbiology and Cancer Center, University of Virginia School of Medicine, Charlottesville, Virginia, VA 22908, USA.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Kulesza
authors.forename: Heather A
authors.initials: HA
authors.lastname: Van Buskirk
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cole
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Reese
authors.forename: M Mitchell
authors.initials: MM
authors.lastname: Smith
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Engel
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal / Q000235:genetics; D051548:Histone Acetyltransferases; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013489:Suppression, Genetic; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D048868:Adaptor Proteins, Signal Transducing; D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051548:Histone Acetyltransferases; D009097:Multienzyme Complexes; D011494:Protein Kinases; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D014157:Transcription Factors; C090575:ADA2 protein, S cerevisiae; C074682:ADR1 protein, S cerevisiae; C106162:HFI1 protein, S cerevisiae; C083323:NGG1 protein, S cerevisiae; C438897:TAF5 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor