Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separa
Author: ["Julia K. Pagan","Antonio Marzio","Mathew J. K. Jones","Anita Saraf","Prasad V. Jallepalli","Laurence Florens","Michael P. Washburn","Michele Pagano"]
Publication: Nature Cell Biology
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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 SCFβTrCP (Skp1–Cul1–F-box protein) ubiquitin ligase complex. Cep68 degradation is initiated by PLK1 phosphorylation of Cep68 on Ser 332, allowing recognition by βTrCP. 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. Pagano and colleagues find that Plk1 and the E3 ubiquitin ligase SCFβTrCP mediate degradation of the centrosome cohesion protein Cep68 and show this mediates removal of Cep215 from the PCM and subsequent centriole separation in late mitosis.
Cite this article
Pagan, J., Marzio, A., Jones, M. et al. Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement and licensing. Nat Cell Biol 17, 31–43 (2015). https://doi.org/10.1038/ncb3076
