HDAC6 and SIRT2 regulate the acetylation state and oncogenic activity of mutant K-RAS.

ABSTRACT:

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Activating point mutations in K-RAS are extremely common in cancers of the lung, colon, and pancreas and are highly predictive of poor therapeutic response. One potential strategy for overcoming the deleterious effects of mutant K-RAS is to alter its posttranslational modification. Although therapies targeting farnesylation have been explored, and have ultimately failed, the therapeutic potential of targeting other modifications remains to be seen. Recently, it was shown that acetylation of lysine 104 attenuates K-RAS transforming activity by interfering with GEF-induced nucleotide exchange. Here, the deacetylases HDAC6 and SIRT2 were shown to regulate the acetylation state of K-RAS in cancer cells. By extension, inhibition of either of these enzymes has a dramatic impac

SUBMITTER: Yang MH 

PROVIDER: S-EPMC3778089 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature