Oncogenic microtubule hyperacetylation through BEX4-mediated sirtuin 2 inhibition.

Cell Death Dis 2016 08 11;7(8):e2336. Epub 2016 Aug 11.

Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea.

Five brain-expressed X-linked (BEX) gene members (BEX1-5) are arranged in tandem on chromosome X, and are highly conserved across diverse species. However, little is known about the function and role of BEX. This study represents a first attempt to demonstrate the molecular details of a novel oncogene BEX4. Among BEX proteins, BEX4 localizes to microtubules and spindle poles, and interacts with α-tubulin (α-TUB) and sirtuin 2 (SIRT2). The overexpression of BEX4 leads to the hyperacetylation of α-TUB by inhibiting SIRT2-mediated deacetylation. Furthermore, we found BEX4 expression conferred resistance to apoptotic cell death but led to acquisition of aneuploidy, and also increased the proliferating potential and growth of tumors. These results suggest that BEX4 overexpression causes an imbalance between TUB acetylation and deacetylation by SIRT2 inhibition and induces oncogenic aneuploidy transformation.

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http://dx.doi.org/10.1038/cddis.2016.240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108325PMC
August 2016
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