Topic
CEP63
About: CEP63 is a research topic. Over the lifetime, 8 publications have been published within this topic receiving 489 citations. The topic is also known as: SCKL6 & centrosomal protein 63.
Papers
TL;DR: It is reported that human Cep63 binds to and recruits Cdk1 to centrosomes, and thereby regulates mitotic entry, providing a physical link between the centrosome and the cell-cycle machinery.
Abstract: Centrosomes are central regulators of mitosis that are often amplified in cancer cells. Centrosomes function both as organizers of the mitotic spindle and as reaction centers to trigger activation of Cdk1 and G2/M transition in the cell cycle, but their functional organization remains incomplete. Recent proteomic studies have identified novel components of the human centrosome including Cep63, a protein of unknown function that Xenopus studies have implicated in mitotic spindle assembly and spindle inactivation after DNA damage. Here, we report that human Cep63 binds to and recruits Cdk1 to centrosomes, and thereby regulates mitotic entry. RNAi-mediated Cep63 depletion in U2OS cancer cells induced polyploidization through mitotic skipping. Elicitation of this phenotype was associated with downregulation of centrosomal Cdk1, mimicking the phenotype induced by direct depletion of Cdk1. In contrast, Cep63 overexpression induced de novo centrosome amplification during cell-cycle interphase. Induction of this phenotype was suppressible by cell treatment with the Cdk inhibitor roscovitine. In a survey of 244 neuroblastoma cases, Cep63 mRNA overexpression was associated with MYCN oncogene amplification and poor prognosis. In cultured cells, Cep63 overexpression was associated with an enhancement in replication-induced DNA breakage. Together, our findings define human Cep63 as a centrosomal recruitment factor for Cdk1 that is essential for mitotic entry, providing a physical link between the centrosome and the cell-cycle machinery. Cancer Res; 71(6); 2129–39. ©2011 AACR.
63 citations
TL;DR: In this paper, the autophagic regulation of centrosome number is shown to be dependent on a centrosomal protein of 63 (Cep63), which is recruited to autophagosomes via interaction with p62, a molecule crucial for selective autophagy.
Abstract: Centrosome number is associated with the chromosome segregation and genomic stability. The ubiquitin-proteasome system is considered to be the main regulator of centrosome number. However, here we show that autophagy also regulates the number of centrosomes. Autophagy-deficient cells carry extra centrosomes. The autophagic regulation of centrosome number is dependent on a centrosomal protein of 63 (Cep63) given that cells lacking autophagy contain multiple Cep63 dots that are engulfed and digested by autophagy in wild-type cells, and that the upregulation of Cep63 increases centrosome number. Cep63 is recruited to autophagosomes via interaction with p62, a molecule crucial for selective autophagy. In vivo, hematopoietic cells from autophagy-deficient and p62-/- mice also contained multiple centrosomes. These results indicate that autophagy controls centrosome number by degrading Cep63.
37 citations
TL;DR: It is hypothesised that CEP63 is particularly important for brain development and might control the proliferation and migration of cells when those two events need to be highly coordinated.
Abstract: Developmental dyslexia is the most common learning disorder in children. Problems in reading and writing are likely due to a complex interaction of genetic and environmental factors, resulting in reduced power of studies of the genetic factors underlying developmental dyslexia. Our approach in the current study was to perform exome sequencing of affected and unaffected individuals within an extended pedigree with a familial form of developmental dyslexia. We identified a two-base mutation, causing a p.R229L amino acid substitution in the centrosomal protein 63 kDa (CEP63), co-segregating with developmental dyslexia in this pedigree. This mutation is novel, and predicted to be highly damaging for the function of the protein. 3D modelling suggested a distinct conformational change caused by the mutation. CEP63 is localised to the centrosome in eukaryotic cells and is required for maintaining normal centriole duplication and control of cell cycle progression. We found that a common polymorphism in the CEP63 gene had a significant association with brain white matter volume. The brain regions were partly overlapping with the previously reported region influenced by polymorphisms in the dyslexia susceptibility genes DYX1C1 and KIAA0319. We hypothesise that CEP63 is particularly important for brain development and might control the proliferation and migration of cells when those two events need to be highly coordinated.
29 citations
TL;DR: Using super-resolution microscopy, this work suggests that the CEP152-CEP63 ring-like structure ensures normal neurodevelopment and that its impairment particularly affects human cerebral cortex growth.
Abstract: Autosomal recessive primary microcephaly (MCPH) is characterized by a substantial reduction in prenatal human brain growth without alteration of the cerebral architecture and is caused by biallelic mutations in genes coding for a subset of centrosomal proteins. Although at least three of these proteins have been implicated in centrosome duplication, the nature of the centrosome dysfunction that underlies the neurodevelopmental defect in MCPH is unclear. Here we report a homozygous MCPH-causing mutation in human CEP63. CEP63 forms a complex with another MCPH protein, CEP152, a conserved centrosome duplication factor. Together, these two proteins are essential for maintaining normal centrosome numbers in cells. Using super-resolution microscopy, we found that CEP63 and CEP152 co-localize in a discrete ring around the proximal end of the parental centriole, a pattern specifically disrupted in CEP63-deficient cells derived from patients with MCPH. This work suggests that the CEP152-CEP63 ring-like structure ensures normal neurodevelopment and that its impairment particularly affects human cerebral cortex growth.
TL;DR: Novel functional interactions among a set of 31 centrosomal proteins are revealed and it is identified that Cep57, Cep63, and Cep152 are parts of a ring-like complex localizing around the proximal end of centrioles, where the cartwheel is located.
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2020 | 1 |
| 2016 | 1 |
| 2015 | 2 |
| 2013 | 1 |
| 2012 | 1 |
| 2011 | 2 |