title: E3 ligase UHRF2 stabilizes the acetyltransferase TIP60 and regulates H3K9ac and H3K14ac via RING finger domain.
abstract: UHRF2 is a ubiquitin-protein ligase E3 that regulates cell cycle, genomic stability and epigenetics. We conducted a co-immunoprecipitation assay and found that TIP60 and HDAC1 interact with UHRF2. We previously demonstrated that UHRF2 regulated H3K9ac and H3K14ac differentially in normal and cancer cells. However, the accurate signal transduction mechanisms were not clear. In this study, we found that TIP60 acted downstream of UHRF2 to regulate H3K9ac and H3K14ac expression. TIP60 is stabilized in normal cells by UHRF2 ubiquitination. However, TIP60 is destabilized in cancer cells. Depletion or inhibition of TIP60 disrupts the regulatory relationship between UHRF2, H3K9ac and H3K14ac. In summary, the findings suggest that UHRF2 mediated the post-translational modification of histones and the initiation and progression of cancer.
authors.affiliation: Department of Cell Biology and Medical Genetics, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Cell Biology and Medical Genetics, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cell Biology and Medical Genetics, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, 400016, China. duanchzhu@gmail.com.
authors.forename: Changzhu
authors.initials: C
authors.lastname: Duan
mesh_terms: D002460:Cell Line; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D054829:RING Finger Domains; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D006657:Histones; D009363:Neoplasm Proteins; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C465619:UHRF2 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: TIP60; UHRF2; acetylation; hepatocellular carcinoma; ubiquitination