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

doi:10.1007/s13238-016-0324-z

Protein Cell

2017, Vol. 8

Issue (3) : 202-218 https://doi.org/10.1007/s13238-016-0324-z

RESEARCH ARTICLE

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

Shengyuan Zeng¹,Yangyang Wang¹,Ting Zhang²,Lu Bai³,Yalan Wang⁴,Changzhu Duan¹(

)

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

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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 UHRF2 TIP60 ubiquitination acetylation hepatocellular carcinoma

Corresponding Author(s): Changzhu Duan

Issue Date: 21 March 2017

Cite this article:

Shengyuan Zeng,Yangyang Wang,Ting Zhang, et al. E3 ligase UHRF2 stabilizes the acetyltransferase TIP60 and regulates H3K9ac and H3K14ac via RING finger domain[J]. Protein Cell, 2017, 8(3): 202-218.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-016-0324-z
https://academic.hep.com.cn/pac/EN/Y2017/V8/I3/202

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