title: Rootletin prevents Cep68 from VHL-mediated proteasomal degradation to maintain centrosome cohesion.
abstract: Centrosome cohesion, mostly regarded as a proteinaceous linker between parental centrioles, ensures the interphase centrosome(s) to function as a single microtubule-organizing center. Maintenance of centrosome cohesion counts on a number of centrosomal linker proteins because depletion of any of those leads to premature centrosome separation in interphase, termed centrosome splitting. However, the underlying mechanisms of the dependence are unknown. Here, we show that absence of Rootletin triggers the von Hippel-Lindau tumour suppressor protein (VHL)-mediated proteasomal degradation of Cep68 and, in turn, results in centrosome splitting. The VHL E3 ligase complex ubiquitinates Cep68 in vitro and in vivo. Co-silencing of Rootletin and VHL reverts Cep68 loss and centrosome splitting. Expression of a stable mutant of Cep68, either diminishing its polyubiquitylation or eliminating binding to β-domain of VHL, also suppresses centrosome splitting provoked by Rootletin depletion. We propose that the archetypal linker protein Rootletin maintains centrosome cohesion in part through inhibition of VHL-mediated Cep68 degradation.
authors.affiliation: Savaid School of Medicine, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Huilong
authors.initials: H
authors.lastname: Yin
authors.affiliation: Savaid School of Medicine, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Weixiao
authors.initials: W
authors.lastname: Liu
authors.affiliation: Savaid School of Medicine, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Dachuan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: leways@ioz.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Savaid School of Medicine, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: yuanli@ucas.ac.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism* / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C527270:CEP68 protein, human; C499237:CROCC protein, human; D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D046988:Proteasome Endopeptidase Complex; C497446:VHL protein, human
keywords: Centrosome cohesion; Centrosome splitting; Cep68; Rootletin; Ubiquitin-proteasome system (UPS); von Hippel-Lindau (VHL)