2. Academic Validation
  3. Oncogenic microtubule hyperacetylation through BEX4-mediated sirtuin 2 inhibition

Oncogenic microtubule hyperacetylation through BEX4-mediated sirtuin 2 inhibition

  • Cell Death Dis. 2016 Aug 11;7(8):e2336. doi: 10.1038/cddis.2016.240.
Jin-Kwan Lee 1,  Janet Lee 2,  Heounjeong Go 3,  Chang Geun Lee 4,  Suhyeon Kim 2,  Hyun-Soo Kim 2,  Hyeseong Cho 5,  Kyeong Sook Choi 5,  Geun-Hyoung Ha 2,  Chang-Woo Lee 1 2
Affiliations

Affiliations

  • 1 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea.
  • 2 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
  • 3 Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
  • 4 Team of Radiation effect Research, Research Center, Dongnam Institute of Radiological and Medical Science, Busan 46033, Korea.
  • 5 Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea.
PMID: 27512957 DOI: 10.1038/cddis.2016.240
Abstract

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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