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Protein Cell. 2017 Mar;8(3):202-218. doi: 10.1007/s13238-016-0324-z. Epub 2016 Oct 14.

E3 ligase UHRF2 stabilizes the acetyltransferase TIP60 and regulates H3K9ac and H3K14ac via RING finger domain.

Author information

1
Department of Cell Biology and Medical Genetics, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, 400016, China.
2
Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
3
Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
4
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, 400016, China.
5
Department of Cell Biology and Medical Genetics, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, 400016, China. duanchzhu@gmail.com.

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.

KEYWORDS:

TIP60; UHRF2; acetylation; hepatocellular carcinoma; ubiquitination

PMID:
27743347
PMCID:
PMC5326618
DOI:
10.1007/s13238-016-0324-z
[Indexed for MEDLINE]
Free PMC Article

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