Critical roles of T-LAK cell-originated protein kinase in cytokinesis.
We previously reported up-regulation of T-LAK cell-originated protein kinase (TOPK), a novel mitotic kinase, in the great majority of breast cancers. Here we report its critical roles in mitosis, especially in cytokinesis. We found that protein phosphatase 1 alpha (PP1alpha) inactivation by cyclin-dependent kinase 1 (CDK1)/cyclin B1 caused enhancement of autophosphorylation of TOPK and resulted in its activation at an early stage of mitosis. Then TOPK interacted with and phosphorylated p97, a member of the AAA+ family of ATPase proteins, through an interaction with p47 protein as an adaptor protein. Interestingly, knockdown of TOPK or p97 in breast cancer cells caused the mitotic failures in the abscission process. This mitotic failure could be rescued by additional exogenous introduction of wild-type TOPK protein, but not by that of its kinase-dead form. Our findings suggest that TOPK is indispensable for cancer cell cytokinesis throughout phosphorylation on p97.
Park
Jae-Hyun
JH
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Nishidate
Toshihiko
T
Nakamura
Yusuke
Y
Katagiri
Toyomasa
T
D000251:Adenosine Triphosphatases / Q000502:physiology; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D016203:CDC2 Protein Kinase / Q000502:physiology; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D056744:Cyclin B1 / Q000502:physiology; D048749:Cytokinesis; D005260:Female; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases; D009687:Nuclear Proteins / Q000502:physiology; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*
C534699:CCNB1 protein, human; D056744:Cyclin B1; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase; D054645:Protein Phosphatase 1; D000251:Adenosine Triphosphatases; C404942:p97 ATPase