title: Oncogenic microtubule hyperacetylation through BEX4-mediated sirtuin 2 inhibition.
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.
authors: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea.
authors: Jin-Kwan
authors: JK
authors: Lee
authors: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
authors: Janet
authors: J
authors: Lee
authors: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.
authors: Heounjeong
authors: 0000-0003-0412-8709
authors: H
authors: Go
authors: Team of Radiation effect Research, Research Center, Dongnam Institute of Radiological and Medical Science, Busan 46033, Korea.
authors: Chang Geun
authors: CG
authors: Lee
authors: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
authors: Suhyeon
authors: S
authors: Kim
authors: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
authors: Hyun-Soo
authors: HS
authors: Kim
authors: Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea.
authors: Hyeseong
authors: 0000-0002-4672-8887
authors: H
authors: Cho
authors: Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea.
authors: Kyeong Sook
authors: KS
authors: Choi
authors: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
authors: Geun-Hyoung
authors: GH
authors: Ha
authors: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea.|Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
authors: Chang-Woo
authors: CW
authors: Lee
mesh_terms: D000107:Acetylation; D000782:Aneuploidy; D000818:Animals; D049109:Cell Proliferation; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D015513:Oncogene Proteins / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D056565:Sirtuin 2 / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: C000623207:BEX4 protein, human; D008869:Microtubule-Associated Proteins; D015513:Oncogene Proteins; D011506:Proteins; D014404:Tubulin; D056565:Sirtuin 2