PMID- 10531039
OWN - NLM
STAT- MEDLINE
DCOM- 19991206
LR  - 20161124
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 9
IP  - 20
DP  - 1999 Oct 21
TI  - Deletion of the Cul1 gene in mice causes arrest in early embryogenesis and
      accumulation of cyclin E.
PG  - 1191-4
AB  - The stability of many proteins is controlled by the ubiquitin proteolytic system,
      which recognizes specific substrates through the action of E3 ubiquitin ligases
      [1]. The SCFs are a recently described class of ubiquitin ligase that target a
      number of cell cycle regulators and other proteins for degradation in both yeast 
      and mammalian cells [2] [3] [4] [5] [6]. Each SCF complex is composed of the core
      protein subunits Skp1, Rbx1 and Cul1 (known as Cdc53 in yeast), and
      substrate-specific adaptor subunits called F-box proteins [2] [3] [4]. To
      understand the physiological role of SCF complexes in mammalian cells, we
      generated mice carrying a deletion in the Cul1 gene. Cul1(-/-) embryos arrested
      around embryonic day 6.5 (E6.5) before the onset of gastrulation. In all cells of
      the mutant embryos, cyclin E protein, but not mRNA, was highly elevated.
      Outgrowths of Cul1(-/-) blastocysts had limited proliferative capacity in vitro
      and accumulated cyclin E in all cells. Within Cul1(-/-) blastocyst cultures,
      trophoblast giant cells continued to endocycle despite the elevated cyclin E
      levels. These results suggest that cyclin E abundance is controlled by SCF
      activity, possibly through SCF-dependent degradation of cyclin E.
FAU - Wang, Y
AU  - Wang Y
AD  - Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute,
      Mount Sinai Hospital, 600 University Avenue, Toronto, M5G 1X5, Canada.
FAU - Penfold, S
AU  - Penfold S
FAU - Tang, X
AU  - Tang X
FAU - Hattori, N
AU  - Hattori N
FAU - Riley, P
AU  - Riley P
FAU - Harper, J W
AU  - Harper JW
FAU - Cross, J C
AU  - Cross JC
FAU - Tyers, M
AU  - Tyers M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Cyclin E)
RN  - 0 (RNA, Messenger)
RN  - EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases)
RN  - EC 6.3.2.- (Peptide Synthases)
SB  - IM
MH  - Animals
MH  - Blastocyst/metabolism
MH  - Cyclin E/genetics/*metabolism
MH  - Embryonic and Fetal Development/*genetics/*physiology
MH  - Female
MH  - Gestational Age
MH  - Mice
MH  - Mice, Knockout
MH  - Peptide Synthases/chemistry/*genetics/*physiology
MH  - Pregnancy
MH  - Protein Structure, Quaternary
MH  - RNA, Messenger/genetics/metabolism
MH  - SKP Cullin F-Box Protein Ligases
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - S0960-9822(00)80024-X [pii]
AID - 10.1016/S0960-9822(00)80024-X [doi]
PST - ppublish
SO  - Curr Biol. 1999 Oct 21;9(20):1191-4. doi: 10.1016/S0960-9822(00)80024-X.