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Oncogenic potential of BEX4 is conferred by Polo-like kinase 1-mediated phosphorylation.

ABSTRACT: The brain-expressed X-linked 4 (BEX4) gene has been recently identified as a mediator of microtubule hyperacetylation through sirtuin 2 inhibition and is highly overexpressed in human cancers. However, the gain-of-function molecular mechanism of the BEX4 gene in human cancers still needs to be elucidated. This study shows that BEX4 colocalizes and interacts with Polo-like kinase 1 (PLK1) at centrosomes, spindle poles, and midbodies, particularly during mitosis. Interestingly, PLK1-mediated phosphorylation upregulates the stability of BEX4 protein, and the PLK1-BEX4 interaction allows abnormal mitotic cells to adapt to aneuploidy rather than undergo apoptotic cell death. In summary, these results suggest that the oncogenicity of BEX4 is conferred by PLK1-mediated phosphorylation, and thus, the BEX4-PLK1 interaction is a novel oncogenic signal that enables the acquisition of chromosomal aneuploidy.

SUBMITTER: Lee JK

PROVIDER: S-EPMC6203768 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Oncogenic potential of BEX4 is conferred by Polo-like kinase 1-mediated phosphorylation.

Lee Jin-Kwan JK Ha Geun-Hyoung GH Kim Hyun-Soo HS Lee Chang-Woo CW

Experimental & molecular medicine 20181022 10

The brain-expressed X-linked 4 (BEX4) gene has been recently identified as a mediator of microtubule hyperacetylation through sirtuin 2 inhibition and is highly overexpressed in human cancers. However, the gain-of-function molecular mechanism of the BEX4 gene in human cancers still needs to be elucidated. This study shows that BEX4 colocalizes and interacts with Polo-like kinase 1 (PLK1) at centrosomes, spindle poles, and midbodies, particularly during mitosis. Interestingly, PLK1-mediated phosp ...[more]

PMID: 30367032

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