A crucial role of SUMOylation in modulating Sirt6 deacetylation of H3 at lysine 56 and its tumor suppressive activity

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 mo...

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Bibliographic Details
Published in:Oncogene 2016-09, Vol.35 (37), p.4949-4956
Main Authors: Cai, J, Zuo, Y, Wang, T, Cao, Y, Cai, R, Chen, F-L, Cheng, J, Mu, J
Format: Article
Language:English
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A549 Cells
Acetylation
Apoptosis
Biosynthesis
c-Myc protein
Cancer
Carcinogenesis
Carcinogenesis - genetics
Cell Biology
Cell proliferation
Cell Proliferation - genetics
Deacetylation
Development and progression
Gene expression
Gene silencing
Genes, Tumor Suppressor
Genetic aspects
Health aspects
Histone deacetylase
Histone Deacetylases - genetics
Human Genetics
Humans
Internal Medicine
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Lysine
Lysine - genetics
Medicine
Medicine & Public Health
Myc protein
NAD
Oncology
Properties
Proto-Oncogene Proteins c-myc - genetics
short-communication
Signaling peptides and proteins
Sirtuins - genetics
Studies
SUMO protein
Sumoylation - genetics
Tumor suppressor genes
Tumorigenesis
Ubiquitin
Ubiquitin-proteasome system
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Summary: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.
ISSN:0950-9232
1476-5594
DOI:10.1038/onc.2016.24