PMID- 10485847
OWN - NLM
STAT- MEDLINE
DCOM- 19991012
LR  - 20190516
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 13
IP  - 17
DP  - 1999 Sep 1
TI  - Components of an SCF ubiquitin ligase localize to the centrosome and regulate the
      centrosome duplication cycle.
PG  - 2242-57
AB  - 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.
FAU - Freed, E
AU  - Freed E
AD  - Departments of Pathology and Microbiology and Immunology, Stanford University
      School of Medicine, Palo Alto, California 94305 USA.
FAU - Lacey, K R
AU  - Lacey KR
FAU - Huie, P
AU  - Huie P
FAU - Lyapina, S A
AU  - Lyapina SA
FAU - Deshaies, R J
AU  - Deshaies RJ
FAU - Stearns, T
AU  - Stearns T
FAU - Jackson, P K
AU  - Jackson PK
LA  - eng
GR  - R01 GM054811/GM/NIGMS NIH HHS/United States
GR  - T32 CA009151/CA/NCI NIH HHS/United States
GR  - CA09151/CA/NCI NIH HHS/United States
GR  - R01 GM54811/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (CDC4 protein, S cerevisiae)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (F-Box Proteins)
RN  - 0 (F-Box-WD Repeat-Containing Protein 7)
RN  - 0 (FBXW7 protein, human)
RN  - 0 (Fbxw7 protein, mouse)
RN  - 0 (NEDD8 Protein)
RN  - 0 (Nedd8 protein, mouse)
RN  - 0 (S-Phase Kinase-Associated Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Tissue Extracts)
RN  - 0 (Ubiquitins)
RN  - EC 2.3.2.23 (CDC34 protein, S cerevisiae)
RN  - EC 2.3.2.23 (CDC34 protein, human)
RN  - EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes)
RN  - EC 2.3.2.23 (Ubiquitin-Protein Ligase Complexes)
RN  - EC 2.3.2.27 (Anaphase-Promoting Complex-Cyclosome)
RN  - EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 6.- (Ligases)
RN  - EC 6.3.2.- (Peptide Synthases)
SB  - IM
MH  - 3T3 Cells
MH  - Anaphase-Promoting Complex-Cyclosome
MH  - Animals
MH  - CHO Cells
MH  - Cell Cycle/*genetics
MH  - Cell Cycle Proteins/genetics/*metabolism
MH  - Centrioles/physiology/ultrastructure
MH  - Centrosome/*enzymology/ultrastructure
MH  - Cricetinae
MH  - *F-Box Proteins
MH  - F-Box-WD Repeat-Containing Protein 7
MH  - Female
MH  - Ligases/genetics/metabolism
MH  - Mice
MH  - NEDD8 Protein
MH  - Ovum
MH  - Peptide Synthases/*metabolism
MH  - S Phase
MH  - S-Phase Kinase-Associated Proteins
MH  - SKP Cullin F-Box Protein Ligases
MH  - Saccharomyces cerevisiae/cytology/physiology
MH  - Saccharomyces cerevisiae Proteins
MH  - Spindle Apparatus/physiology/ultrastructure
MH  - Tissue Extracts/physiology
MH  - Ubiquitin-Conjugating Enzymes
MH  - *Ubiquitin-Protein Ligase Complexes
MH  - *Ubiquitin-Protein Ligases
MH  - Ubiquitins/metabolism
MH  - Xenopus laevis
PMC - PMC316987
EDAT- 1999/09/15 00:00
MHDA- 1999/09/15 00:01
CRDT- 1999/09/15 00:00
PHST- 1999/09/15 00:00 [pubmed]
PHST- 1999/09/15 00:01 [medline]
PHST- 1999/09/15 00:00 [entrez]
AID - 10.1101/gad.13.17.2242 [doi]
PST - ppublish
SO  - Genes Dev. 1999 Sep 1;13(17):2242-57. doi: 10.1101/gad.13.17.2242.