An NAD+-Dependent Deacetylase SIRT7 Promotes HCC Development Through Deacetylation of USP39

Ling Dong; Le Yu; Hui Li; Lei Shi; Zhong Luo; Huakan Zhao; Zhaojian Liu; Guobing Yin; Xiaohua Yan; Zhenghong Lin

doi:10.1016/j.isci.2020.101351

An NAD⁺-Dependent Deacetylase SIRT7 Promotes HCC Development Through Deacetylation of USP39

iScience. 2020 Aug 21;23(8):101351. doi: 10.1016/j.isci.2020.101351. Epub 2020 Jul 9.

Authors

Ling Dong¹, Le Yu¹, Hui Li¹, Lei Shi¹, Zhong Luo¹, Huakan Zhao², Zhaojian Liu³, Guobing Yin⁴, Xiaohua Yan⁵, Zhenghong Lin⁶

Affiliations

¹ School of Life Sciences, Chongqing University, Chongqing 401331, P.R. China.
² Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
³ Department of Cell Biology, Shandong University School of Medicine, Jinan 250012, P.R. China.
⁴ Department of Breast, Thyroid, Pancreatic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
⁵ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang 330006, Jiangxi, P.R. China. Electronic address: yanxiaohua@ncu.edu.cn.
⁶ School of Life Sciences, Chongqing University, Chongqing 401331, P.R. China. Electronic address: zhenghonglin@cqu.edu.cn.

Abstract

Ubiquitin specific protease 39 (USP39), an ortholog of Sad1p in yeast, is essential for spliceosome assembly during pre-mRNA splicing in human. Although it is known that USP39 is upregulated and plays an oncogenic role in hepatocellular carcinoma (HCC), the underlying mechanism remains unknown. The results of this study demonstrated that USP39 can be acetylated by the histone acetyltransferase MYST1, which is required for its proteasome-mediated degradation by Von Hippel-Lindau protein. In HCC cells, USP39 interacts with and is deacetylated by the lysine deacetylase sirtuin 7 (SIRT7). Notably, the deacetylation of USP39 by SIRT7 promotes its stability and thereby accelerates HCC cell proliferation and tumorigenesis in vitro and in vivo. Our data demonstrated a novel mechanism by which SIRT7 modulates the deacetylation of USP39 to promote HCC development, thus providing an effective anti-tumor therapeutic strategy for HCC.

Keywords: Cancer; Cell Biology; Molecular Biology.