p300 does not require its acetylase activity to stimulate p73 function.
We previously reported that p73, like p53, utilizes p300 or cAMP-response element-binding protein-binding protein as its coactivator. Here, we extended this work by further examining whether the intrinsic acetylase activity of p300 is necessary for stimulating p73 function. Although p300 acetylated the C-terminal fragment of p73 (amino acids 311-636) in vitro, it was unable to efficiently acetylate the full-length p73. Consistently, p300 did not acetylate p73 in vivo when both the proteins were overexpressed in cells. Also, an acetylase-defective mutant p300 named p300AT2 was able to elevate p73-dependent transcription in cells. p300 associated with p73 when forming DNA-protein complexes and stabilized p73 proteins. These results demonstrate that p300 does not need its acetylase activity to be a coactivator of p73.
Zeng
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Department of Biochemistry and Molecular Biology, Oregon Health Science University, Portland, Oregon 97201, USA.
Lee
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Zhang
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Lu
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D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D051548:Histone Acetyltransferases; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C000606460:TP73 protein, human