Ad E1A 243R oncoprotein promotes association of proto-oncogene product MYC with the NuA4/Tip60 complex via the E1A N-terminal repression domain.
The adenovirus E1A 243R oncoprotein targets TRRAP, a scaffold protein that assembles histone acetyltransferase (HAT) complexes, such as the NuA4/Tip60 complex which mediates transcriptional activity of the proto-oncogene MYC and helps determine the cancer cell phenotype. How E1A transforms cells through TRRAP remains obscure. We performed proteomic analysis with the N-terminal transcriptional repression domain of E1A 243R (E1A 1-80) and showed that E1A 1-80 interacts with TRRAP, p400, and three other members of the NuA4 complex - DMAP1, RUVBL1 and RUVBL2 - not previously shown to associate with E1A 243R. E1A 1-80 interacts with these NuA4 components and MYC through the E1A TRRAP-targeting domain. E1A 243R association with the NuA4 complex was demonstrated by co-immunoprecipitation and analysis with DMAP1, Tip60, and MYC. Significantly, E1A 243R promotes association of MYC/MAX with the NuA4/Tip60 complex, implicating the importance of the MYC/NuA4 pathway in cellular transformation by both MYC and E1A.
Department of Microbiology and Molecular Immunology/Institute for Molecular Virology, Saint Louis University School of Medicine, Doisy Research Center, St. Louis, MO 63104, USA.
Ling-Jun
LJ
Zhao
Department of Microbiology and Molecular Immunology/Institute for Molecular Virology, Saint Louis University School of Medicine, Doisy Research Center, St. Louis, MO 63104, USA.
Paul M
PM
Loewenstein
Department of Microbiology and Molecular Immunology/Institute for Molecular Virology, Saint Louis University School of Medicine, Doisy Research Center, St. Louis, MO 63104, USA. Electronic address: green@slu.edu.
Maurice
M
Green
D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D040901:Proteomics / Q000379:methods; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; C000715470:MAS1 protein, human; D046912:Multiprotein Complexes; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5
243R; DMAP1; E1A 1-80; NuA4; RUVBL1; RUVBL2; TRRAP; Tip60
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