PMID- 10500095
OWN - NLM
STAT- MEDLINE
DCOM- 19991025
LR  - 20220331
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 13
IP  - 18
DP  - 1999 Sep 15
TI  - Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian
      cells.
PG  - 2375-87
AB  - Cyclin E is an unstable protein that is degraded in a ubiquitin- and proteasome- 
      dependent pathway. Two factors stimulate cyclin E ubiquitination in vivo: when it
      is free of its CDK partner, and when it is phosphorylated on threonine 380. We
      pursued the first of these pathways by using a two-hybrid screen to identify
      proteins that could bind only to free cyclin E. This resulted in the isolation of
      human Cul-3, a member of the cullin family of E3 ubiquitin-protein ligases. We
      found that Cul-3 was bound to cyclin E but not to cyclin E-Cdk2 complexes in
      mammalian cells, and that overexpression of Cul-3 increased ubiquitination of
      cyclin E but not other cyclins. Conversely, deletion of the Cul-3 gene in mice
      caused increased accumulation of cyclin E protein, and had cell-type-specific
      effects on S-phase regulation. In the extraembryonic ectoderm, in which cells
      undergo a standard mitotic cycle, there was a greatly increased number of cells
      in S phase. In the trophectoderm, in which cells go through endocycles, there was
      a block to entry into S phase. The SCF pathway, which targets cyclins for
      ubiquitination on the basis of their phosphorylation state, and the Cul-3
      pathway, which selects cyclin E for ubiquitination on the basis of its assembly
      into CDK complexes, may be complementary ways to control cyclin abundance.
FAU - Singer, J D
AU  - Singer JD
AD  - Division of Basic Sciences, Howard Hughes Medical Institute, Seattle, Washington 
      98109 USA.
FAU - Gurian-West, M
AU  - Gurian-West M
FAU - Clurman, B
AU  - Clurman B
FAU - Roberts, J M
AU  - Roberts JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (CUL3 protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cul3 protein, mouse)
RN  - 0 (Cullin Proteins)
RN  - 0 (Cyclin E)
RN  - 0 (NEDD8 Protein)
RN  - 0 (NEDD8 protein, human)
RN  - 0 (Nedd8 protein, mouse)
RN  - 0 (Ubiquitins)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Blastocyst/cytology
MH  - Cell Cycle Proteins/*genetics/*physiology
MH  - Cloning, Molecular
MH  - *Cullin Proteins
MH  - Cyclin E/*metabolism
MH  - Embryo, Mammalian/anatomy & histology
MH  - Gene Expression Regulation, Developmental
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Models, Genetic
MH  - NEDD8 Protein
MH  - Phenotype
MH  - Protein Binding
MH  - S Phase/*physiology
MH  - Saccharomyces cerevisiae/metabolism
MH  - Signal Transduction
MH  - Tissue Distribution
MH  - Tumor Cells, Cultured
MH  - Ubiquitins/*metabolism
PMC - PMC317026
EDAT- 1999/09/29 00:00
MHDA- 1999/09/29 00:01
CRDT- 1999/09/29 00:00
PHST- 1999/09/29 00:00 [pubmed]
PHST- 1999/09/29 00:01 [medline]
PHST- 1999/09/29 00:00 [entrez]
AID - 10.1101/gad.13.18.2375 [doi]
PST - ppublish
SO  - Genes Dev. 1999 Sep 15;13(18):2375-87. doi: 10.1101/gad.13.18.2375.