The peptidyl-prolyl isomerase Pin1 regulates cytokinesis through Cep55.
Failure of cytokinesis results in tetraploidy and can increase the genomic instability frequently observed in cancer. The peptidyl-prolyl isomerase Pin1, which is deregulated in many tumors, regulates several processes, including cell cycle progression. Here, we show a novel role for Pin1 in cytokinesis. Pin1 knockout mouse embryonic fibroblasts show a cytokinesis delay, and depletion of Pin1 from HeLa cells also causes a cytokinesis defect. Furthermore, we provide evidence that Pin1 localizes to the midbody ring and regulates the final stages of cytokinesis by binding to centrosome protein 55 kDa (Cep55), an essential component of this ring. This interaction induces Polo-like kinase 1-mediated phosphorylation of Cep55, which is critical for the function of Cep55 during cytokinesis. Importantly, Pin1 knockdown does not enhance the cytokinesis defect in Cep55-depleted cells, indicating that Pin1 and Cep55 act in the same pathway. These data are the first evidence that Pin1 regulates cytokinesis and may provide a mechanistic explanation as to how pathologic levels of Pin1 can stimulate tumorigenesis.
van der Horst
Armando
A
Queensland Institute of Medical Research, Brisbane, Australia.
Khanna
Kum Kum
KK
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured; D048749:Cytokinesis / Q000187:drug effects / Q000235:genetics*; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008954:Models, Biological; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000494:pharmacology
D018797:Cell Cycle Proteins; C505378:Cep55 protein, human; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse