Confirming the role of SIRT6 as tumor suppressor in Cancer

 

Scientists have previously identified the histone deacetylase SIRT6 as a key tumor suppressor, yet whether point mutations are selected for in cancer remains unclear.

They characterized naturally occurring patient-derived SIRT6 mutations in this study published in Cell Reports. Strikingly, all the mutations significantly affected either stability or catalytic activity of SIRT6, indicating that these mutations were selected for in these tumors.

Further, the mutant proteins failed to rescue sirt6 knockout (SIRT6 KO) cells, as measured by the levels of histone acetylation at glycolytic genes and their inability to rescue the tumorigenic potential of these cells.

Notably, the main activity affected in the mutants was histone deacetylation rather than demyristoylation, pointing to the former as the main tumor-suppressive function for SIRT6.

These results identified cancer-associated point mutations in SIRT6, cementing its function as a tumor suppressor in human cancer.

http://www.cell.com/cell-reports/abstract/S2211-1247(15)01033-5

Edited October 22nd 2015