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
Affiliations
Ling Dong
School of Life Sciences, Chongqing University, Chongqing 401331, P.R. China
Le Yu
School of Life Sciences, Chongqing University, Chongqing 401331, P.R. China
Hui Li
School of Life Sciences, Chongqing University, Chongqing 401331, P.R. China
Lei Shi
School of Life Sciences, Chongqing University, Chongqing 401331, P.R. China
Zhong Luo
School of Life Sciences, Chongqing University, Chongqing 401331, P.R. China
Huakan Zhao
Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, P.R. China
Zhaojian Liu
Department of Cell Biology, Shandong University School of Medicine, Jinan 250012, P.R. China
Guobing Yin
Department of Breast, Thyroid, Pancreatic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
Xiaohua Yan
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang 330006, Jiangxi, P.R. China; Corresponding author
Zhenghong Lin
School of Life Sciences, Chongqing University, Chongqing 401331, P.R. China; Corresponding author
Summary: 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.
