Abstract
The cellular protein AMF-1 (Gps2) positively modulates gene expression by the papillomavirus E2 protein (D. E. Breiding et al., Mol. Cell. Biol. 17:7208-7219, 1997). We show here that AMF-1 also binds the transcriptional coactivator p300 in vitro and in vivo. E2 interacted weakly with p300. These observations led to a model in which AMF-1 recruits p300 into a complex with E2. Cotransfection of AMF-1 or p300 stimulated levels of E2-dependent transcription, while cotransfection of both AMF-1 and p300 showed an additive effect. The functional significance of p300 recruitment for E2 transactivation was evidenced by repression of E2-activated transcription by adenovirus E1A, which inhibits both coactivator and acetylase activities of p300. Antibodies to AMF-1 or E2 immunoprecipitated histone acetylase activity from cell lysates. Western blotting using antibody against acetyl-lysine failed to detect acetylation of AMF-1 or E2 in complex with p300. These results suggest that AMF-1 facilitates the recruitment of p300 and its histone acetylase activity into complexes with E2 and represents a novel mechanism of transcriptional activation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylation
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Adenovirus E1A Proteins / genetics
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Adenovirus E1A Proteins / metabolism
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Animals
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Binding Sites
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Bovine papillomavirus 1*
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Cattle
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Cell Line
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Chemical Precipitation
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Fungal Proteins / genetics
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Fungal Proteins / metabolism*
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Histones / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Oncogene Proteins, Viral / genetics
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Oncogene Proteins, Viral / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins*
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Spodoptera / cytology
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcriptional Activation
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Tumor Cells, Cultured
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Viral Proteins / genetics
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Viral Proteins / metabolism*
Substances
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Adenovirus E1A Proteins
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DNA-Binding Proteins
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E1 protein, Bovine papillomavirus
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E2 protein, Bovine papillomavirus
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E2 protein, Human papillomavirus type 16
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Fungal Proteins
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GPS2 protein, human
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Histones
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Intracellular Signaling Peptides and Proteins
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Nuclear Proteins
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Oncogene Proteins, Viral
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Recombinant Fusion Proteins
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Repressor Proteins
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Trans-Activators
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Viral Proteins