Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement and licensing Journal Article
| Authors: | Pagan, J. K.; Marzio, A.; Jones, M. J. K.; Saraf, A.; Jallepalli, P. V.; Florens, L.; Washburn, M. P.; Pagano, M. |
| Article Title: | Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement and licensing |
| Abstract: | An intercentrosomal linker keeps a cell's two centrosomes joined together until it is dissolved at the onset of mitosis. A second connection keeps daughter centrioles engaged to their mothers until they lose their orthogonal arrangement at the end of mitosis. Centriole disengagement is required to license centrioles for duplication. We show that the intercentrosomal linker protein Cep68 is degraded in prometaphase through the SCF Î 2TrCP (Skp1-Cul1-F-box protein) ubiquitin ligase complex. Cep68 degradation is initiated by PLK1 phosphorylation of Cep68 on Ser 332, allowing recognition by Î 2TrCP. We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. Cep68 and PCNT bind to different pools of Cep215. We propose that Cep68 degradation allows Cep215 removal from the peripheral PCM preventing centriole separation following disengagement, whereas PCNT cleavage mediates Cep215 removal from the core of the PCM to inhibit centriole disengagement and duplication. © 2015 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | protein phosphorylation; unclassified drug; human cell; complex formation; serine; ubiquitin protein ligase; protein degradation; protein protein interaction; cell protein; protein binding; protein interaction; polo like kinase 1; molecular recognition; cell separation; protein cleavage; centriole; scaffold protein; prometaphase; f box protein; human; priority journal; article; pericentrin; pericentriolar region; protein skp1; protein betatrcp; protein cep215; protein cep68; protein cul1 |
| Journal Title: | Nature Cell Biology |
| Volume: | 17 |
| Issue: | 1 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2015-01-01 |
| Start Page: | 31 |
| End Page: | 43 |
| Language: | English |
| DOI: | 10.1038/ncb3076 |
| PROVIDER: | scopus |
| PMCID: | PMC4415623 |
| PUBMED: | 25503564 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 October 2016 -- Source: Scopus |
