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PKM2 Regulates Chromosome Segregation and Mitosis Progression of Tumor Cells

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

Mol Cell. 2014 Jan 9;53(1):75-87.

PMID: 24316223

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42411980	PKM1 active human			Price

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