Reciprocal interaction between SIRT6 and APC/C regulates genomic stability.
SIRT6 is an NAD+-dependent deacetylase that plays an important role in mitosis fidelity and genome stability. In the present study, we found that SIRT6 overexpression leads to mitosis defects and aneuploidy. We identified SIRT6 as a novel substrate of anaphase-promoting complex/cyclosome (APC/C), which is a master regulator of mitosis. Both ... CDH1 and CDC20, co-activators of APC/C, mediated SIRT6 degradation via the ubiquitination-proteasome pathway. Reciprocally, SIRT6 also deacetylated CDH1 at lysine K135 and promoted its degradation, resulting in an increase in APC/C-CDH1-targeted substrates, dysfunction in centrosome amplification, and chromosome instability. Our findings demonstrate the importance of SIRT6 for genome integrity during mitotic progression and reveal how SIRT6 and APC/C cooperate to drive mitosis.
Mesh Terms:
Anaphase-Promoting Complex-Cyclosome, Antigens, CD, Cadherins, Cdc20 Proteins, Cell Cycle Proteins, Cell Line, Cell Line, Tumor, Chromosomal Instability, HeLa Cells, Humans, Protein Binding, Sirtuins
Anaphase-Promoting Complex-Cyclosome, Antigens, CD, Cadherins, Cdc20 Proteins, Cell Cycle Proteins, Cell Line, Cell Line, Tumor, Chromosomal Instability, HeLa Cells, Humans, Protein Binding, Sirtuins
Sci Rep
Date: Dec. 09, 2020
PubMed ID: 34244565
View in: Pubmed Google Scholar
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