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Mol Cell. 2014 Jan 9;53(1):75-87. doi: 10.1016/j.molcel.2013.11.001. Epub 2013 Dec 5.

PKM2 regulates chromosome segregation and mitosis progression of tumor cells.

Author information

1
Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
2
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
3
Laboratory of Tumor Targeted Therapy, Key Laboratory of System Biology, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.
4
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
5
Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA. Electronic address: zhiminlu@mdanderson.org.

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.

PMID:
24316223
PMCID:
PMC3955203
DOI:
10.1016/j.molcel.2013.11.001
[Indexed for MEDLINE]
Free PMC Article

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