title: A crucial role of SUMOylation in modulating Sirt6 deacetylation of H3 at lysine 56 and its tumor suppressive activity.
abstract: Sirt6 is a histone deacetylase with NAD(+)-dependent activity. Sirt6 has been shown as a tumor suppressor partially via inhibiting the expression of c-Myc target genes and ribosome biogenesis. However, how to regulate Sirt6 activity is largely unknown. In this study, we identify that Sirt6 can be modified by small ubiquitin-like modifier. Sirt6 SUMOylation deficiency specifically decreases its deacetylation of H3K56 but not H3K9 in vivo. Mechanistically, we find that SUMOylation deficiency decreases Sirt6 binding with c-Myc, decreasing Sirt6 occupancy on the locus of c-Myc target genes. Therefore, Sirt6 SUMOylation deficiency reduces its deacetylation of H3k56 and its repression of c-Myc target genes. Moreover, Sirt6 SUMOylation deficiency reduces its suppression of cell proliferation and tumorigenesis. Thus, these results reveal that SUMOylation has an important role in regulation of Sirt6 deacetylation on H3K56, as well as its tumor suppressive activity.
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: R
authors.initials: R
authors.lastname: Cai
authors.affiliation: Shanghai Third People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: F-L
authors.initials: FL
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Mu
mesh_terms: D000072283:A549 Cells; D000107:Acetylation; D063646:Carcinogenesis / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008239:Lysine / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D037761:Sirtuins / Q000235:genetics*; D058207:Sumoylation / Q000235:genetics
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C516592:SIRT6 protein, human; D037761:Sirtuins; D006655:Histone Deacetylases; D008239:Lysine