title: TRIM29 negatively regulates p53 via inhibition of Tip60.
abstract: Ataxia-telangiectasia (AT) is an autosomal recessive genetic disease characterized by immunological deficiencies, neurological degeneration, developmental abnormalities and an increased risk of cancer. Ataxia-telangiectasia group D (ATDC) was initially described as a gene related to AT. Ataxia-telangiectasia group D, also known as TRIM29, is structurally a member of the tripartite motif (TRIM) family of proteins, some of which have been reported to be highly expressed in some human carcinomas, but the involvement of TRIM29 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that TRIM29 binds to Tip60, which has been reported as a cellular acetyltransferase protein. Overexpression of TRIM29 promoted degradation and changed localization of Tip60 and reduced acetylation of p53 at lysine 120 by Tip60, resulting in enhancement of cell growth and transforming activity. In addition, we found that TRIM29 suppresses apoptosis induced by UV irradiation in HCT116 cell lines. These findings suggest that TRIM29 functions as an oncogene that promotes tumor growth.
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sho
authors.forename: Tadasuke
authors.initials: T
authors.lastname: Tsukiyama
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Sato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondo
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Takashi
authors.initials: T
authors.lastname: Saku
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008239:Lysine / Q000378:metabolism; D000074443:Lysine Acetyltransferase 5; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D004268:DNA-Binding Proteins; C087296:TRIM29 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; D008239:Lysine