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

Overview

Journal iScience

Publisher Cell Press

Date 2020 Jul 26

PMID 32711345

Citations 22

Authors

Ling Dong

Le Yu

Hui Li

Lei Shi

Zhong Luo

Huakan Zhao

Zhaojian Liu

Guobing Yin

Xiaohua Yan

Zhenghong Lin

Affiliations

Soon will be listed here.

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.

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