西亞試劑：PKM2 Regulates Chromosome Segregation and Mitosis Progressi

PKM2 Regulates Chromosome Segregation and Mitosis Progression of Tumor Cells

Yuhui Jiang, Xinjian Li, Weiwei Yang, David H. Hawke, Yanhua Zheng, Yan Xia, Kenneth Aldape, Chongyang Wei, Fang Guo, Yan Chen, Zhimin Lu.

Tumor-specific pyruvate kinase M2 (PKM2) is instrumental in both aerobic glycolysis and gene transcription. PKM2 regulates G1-S phase transition by controlling cyclin D1 expression. However, it is not known whether PKM2 directly controls cell-cycle progression. We show here that PKM2, but not PKM1, binds to the spindle checkpoint protein Bub3 during mitosis and phosphorylates Bub3 at Y207. This phosphorylation is required for Bub3-Bub1 complex recruitment to kinetochores, where it interacts with Blinkin and is essential for correct kinetochore-microtubule attachment, mitotic/spindle-assembly checkpoint, accurate chromosome segregation, cell survival and proliferation, and active EGF receptor-induced brain tumorigenesis. In addition, the level of Bub3 Y207 phosphorylation correlated with histone H3-S10 phosphorylation in human glioblastoma specimens and with glioblastoma prognosis. These findings highlight the role of PKM2 as a protein kinase controlling the fidelity of chromosome segregation, cell-cycle progression, and tumorigenesis.

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