SPOP promotes SIRT2 degradation and suppresses non-small cell lung cancer cell growth.
SIRT2 is a NAD-dependent deacetylase and inhibition of SIRT2 has a broad anticancer activity. Here we report that SPOP binds to SIRT2 and mediates its degradation by the 26S proteasome, which can be blocked by MG132 treatment. We also found that the levels of SPOP significantly decreased, while the levels ... of SIRT2 significantly increased in non-small cell lung cancer (NSCLC) cell lines, compared to normal bronchial epithelial cell line and NSCLC specimens, compared to the paired non-tumor lung tissue. Furthermore, SPOP can suppress NSCLC cell growth. Notably, mutations in NSCLC inhibit the abilities of SPOP to degrade SIRT2 and suppress NSCLC cell growth. These results reveal a novel regulation of SIRT2 by SPOP mediated degradation, which is important for the growth of lung tumor cells.
Mesh Terms:
A549 Cells, Carcinoma, Non-Small-Cell Lung, Cell Line, Cell Line, Tumor, Cell Proliferation, Gene Knockdown Techniques, Humans, Lung Neoplasms, Nuclear Proteins, Point Mutation, Proteasome Endopeptidase Complex, Protein Binding, Proteolysis, Repressor Proteins, Respiratory Mucosa, Sirtuin 2
A549 Cells, Carcinoma, Non-Small-Cell Lung, Cell Line, Cell Line, Tumor, Cell Proliferation, Gene Knockdown Techniques, Humans, Lung Neoplasms, Nuclear Proteins, Point Mutation, Proteasome Endopeptidase Complex, Protein Binding, Proteolysis, Repressor Proteins, Respiratory Mucosa, Sirtuin 2
Biochem. Biophys. Res. Commun.
Date: Dec. 05, 2016
PubMed ID: 28073696
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