title: PKM2 regulates chromosome segregation and mitosis progression of tumor cells.
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.
authors: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Yuhui
authors: Y
authors: Jiang
authors: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Xinjian
authors: X
authors: Li
authors: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Weiwei
authors: W
authors: Yang
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: David H
authors: DH
authors: Hawke
authors: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Yanhua
authors: Y
authors: Zheng
authors: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Yan
authors: Y
authors: Xia
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Kenneth
authors: K
authors: Aldape
authors: Laboratory of Tumor Targeted Therapy, Key Laboratory of System Biology, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.
authors: Chongyang
authors: C
authors: Wei
authors: Laboratory of Tumor Targeted Therapy, Key Laboratory of System Biology, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.
authors: Fang
authors: F
authors: Guo
authors: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Yan
authors: Y
authors: Chen
authors: 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.
authors: Zhimin
authors: Z
authors: Lu
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000201:enzymology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D008941:Spindle Apparatus / Q000201:enzymology / Q000235:genetics; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C489444:BUB3 protein, human