PMID- 10375532
OWN - NLM
STAT- MEDLINE
DCOM- 19990820
LR  - 20190728
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 9
IP  - 12
DP  - 1999 Jun 17
TI  - p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex
      through phosphorylated Thr187 in p27.
PG  - 661-4
AB  - Many tumorigenic processes affect cell-cycle progression by their effects on the 
      levels of the cyclin-dependent kinase inhibitor p27(Kip1) [1,2]. The
      phosphorylation- and ubiquitination-dependent proteolysis of p27 is implicated in
      control of the G1-S transition in the cell cycle [3-6]. To determine the factors 
      that control p27 stability, we established a cell-free extract assay that
      recapitulates the degradation of p27. Phosphorylation of p27 at Thr187 was
      essential for its degradation. Degradation was also dependent on SCF(Skp2), a
      protein complex implicated in targeting phosphorylated proteins for
      ubiquitination [7-10]. Immunodepletion of components of the complex - Cul-1,
      Skp1, or Skp2 - from the extract abolished p27 degradation, while addition of
      purified SCF(Skp2) to Skp2- depleted extract restored the capacity to degrade
      p27. A specific association was observed between Skp2 and a p27 carboxy-terminal 
      peptide containing phosphorylated Thr187, but not between Skp2 and the
      non-phosphorylated peptide. Skp2-dependent associations between Skp1 or Cul-1 and
      the p27 phosphopeptide were also detected. Isolated SCF(Skp2) contained an E3
      ubiquitin ligase activity towards p27. Our data thus suggest that SCF(Skp2)
      specifically targets p27 for degradation during cell-cycle progression.
FAU - Tsvetkov, L M
AU  - Tsvetkov LM
AD  - Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New
      Haven, Connecticut 06520, USA.
FAU - Yeh, K H
AU  - Yeh KH
FAU - Lee, S J
AU  - Lee SJ
FAU - Sun, H
AU  - Sun H
FAU - Zhang, H
AU  - Zhang H
LA  - eng
GR  - CA72878/CA/NCI 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  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (Ubiquitins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 2ZD004190S (Threonine)
RN  - EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases)
RN  - EC 6.3.2.- (Peptide Synthases)
SB  - IM
MH  - Cell Cycle
MH  - *Cell Cycle Proteins
MH  - Cell-Free System
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - HeLa Cells
MH  - Humans
MH  - Microtubule-Associated Proteins/chemistry/*metabolism
MH  - Peptide Synthases/genetics/*metabolism
MH  - Phosphorylation
MH  - Recombination, Genetic
MH  - SKP Cullin F-Box Protein Ligases
MH  - Threonine/chemistry/metabolism
MH  - *Tumor Suppressor Proteins
MH  - Ubiquitins/*metabolism
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - S0960-9822(99)80290-5 [pii]
AID - 10.1016/s0960-9822(99)80290-5 [doi]
PST - ppublish
SO  - Curr Biol. 1999 Jun 17;9(12):661-4. doi: 10.1016/s0960-9822(99)80290-5.