Pagan Julia K, Marzio Antonio, Jones Mathew J K, Saraf Anita, Jallepalli Prasad V, Florens Laurence, Washburn Michael P, Pagano Michele
Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York 10065, USA.
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue New York 10065, USA.
Nat Cell Biol. 2015 Jan;17(1):31-43. doi: 10.1038/ncb3076. Epub 2014 Dec 15.
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(βTrCP) (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.
中心体间连接蛋白使细胞的两个中心体保持连接在一起，直到在有丝分裂开始时被溶解。另一种连接使子代中心粒与其母代中心粒保持连接，直到它们在有丝分裂末期失去正交排列。中心粒脱离是中心粒进行复制所必需的。我们发现，中心体间连接蛋白Cep68在有丝分裂前期通过SCF(βTrCP)（Skp1-Cul1-F盒蛋白）泛素连接酶复合物被降解。Cep68的降解由PLK1在Ser 332位点对Cep68的磷酸化引发，从而使其能被βTrCP识别。我们还发现，Cep68与Cep215（也称为Cdk5Rap2）和PCNT（也称为中心体周围蛋白）形成复合物，这两种中心粒周围物质（PCM）蛋白参与中心粒连接。Cep68和PCNT与不同的Cep215池结合。我们提出，Cep68的降解使Cep215从外周PCM中去除，从而防止脱离后的中心粒分离，而PCNT的切割介导Cep215从PCM核心中去除，以抑制中心粒脱离和复制。
