title: TOPK and PTEN participate in CHFR mediated mitotic checkpoint.
abstract: Mitotic progression is regulated by co-ordinated action of several proteins and is crucial for the maintenance of genomic stability. CHFR (Check point protein with FHA and RING domains) is an E3 ubiquitin ligase and a checkpoint protein that regulates entry into mitosis. But the molecular players involved in CHFR mediated mitotic checkpoint are not completely understood. In this study, we identified TOPK/PBK, a serine/threonine kinase and PTEN, a lipid phosphatase to play an important role in CHFR mediated mitotic transitions. We demonstrated that CHFR ubiquitinates and regulates TOPK levels, which is essential for its checkpoint function. Moreover, TOPK phosphorylates and inactivates PTEN, which in turn activates Akt that leads to proper G2/M progression. Collectively, our results reveal TOPK and PTEN as new players in CHFR mediated mitotic checkpoint.
authors.affiliation: Laboratory of Cell Death & Cell Survival, Centre for DNA Fingerprinting and Diagnostics (CDFD), Nampally, Hyderabad 500001, India.
authors.forename: Swapnil R
authors.initials: SR
authors.lastname: Shinde
authors.forename: Narmadha Reddy
authors.initials: NR
authors.lastname: Gangula
authors.forename: Sridhar
authors.initials: S
authors.lastname: Kavela
authors.forename: Vimal
authors.initials: V
authors.lastname: Pandey
authors.forename: Subbareddy
authors.initials: S
authors.lastname: Maddika
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D008938:Mitosis; D009363:Neoplasm Proteins / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D000075223:Poly-ADP-Ribose Binding Proteins; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D025801:Ubiquitin; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Akt; Chfr; E3 ligase; Mitosis; PTEN; TOPK