Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-12346
Genes Dev. September 1, 1999; 13 (17): 2242-57.

Components of an SCF ubiquitin ligase localize to the centrosome and regulate the centrosome duplication cycle.

Freed E , Lacey KR , Huie P , Lyapina SA , Deshaies RJ , Stearns T , Jackson PK .


Abstract
Centrosomes organize the mitotic spindle to ensure accurate segregation of the chromosomes in mitosis. The mechanism that ensures accurate duplication and separation of the centrosomes underlies the fidelity of chromosome segregation, but remains unknown. In Saccharomyces cerevisiae, entry into S phase and separation of spindle pole bodies each require CDC4 and CDC34, which encode components of an SCF (Skp1-cullin-F-box) ubiquitin ligase, but a direct (SCF) connection to the spindle pole body is unknown. Using immunofluorescence microscopy, we show that in mammalian cells the Skp1 protein and the cullin Cul1 are localized to interphase and mitotic centrosomes and to the cytoplasm and nucleus. Deconvolution and immunoelectron microscopy suggest that Skp1 forms an extended pericentriolar structure that may function to organize the centrosome. Purified centrosomes also contain Skp1, and Cul1 modified by the ubiquitin-like molecule NEDD8, suggesting a role for NEDD8 in targeting. Using an in vitro assay for centriole separation in Xenopus extracts, antibodies to Skp1 or Cul1 block separation. Proteasome inhibitors block both centriole separation in vitro and centrosome duplication in Xenopus embryos. We identify candidate centrosomal F-box proteins, suggesting that distinct SCF complexes may direct proteolysis of factors mediating multiple steps in the centrosome cycle.

PubMed ID: 10485847
PMC ID: PMC316987
Article link: Genes Dev.
Grant support: CA09151 NCI NIH HHS , CA09151 NCI NIH HHS , CA09151 NCI NIH HHS , CA09151 NCI NIH HHS , CA09151 NCI NIH HHS , CA09151 NCI NIH HHS , R01 GM54811 NIGMS NIH HHS

Genes referenced: cdc34 cul1 fbxw7 nedd8 skp1
Antibodies referenced:

My Xenbase: [ Log-in / Register ]
version: [3.2.2]


Major funding for Xenbase is provided by the National Institute of Child Health and Human Development, grant P41 HD064556