PMID- 10559916
OWN - NLM
STAT- MEDLINE
DCOM- 19991208
LR  - 20191103
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 1
IP  - 4
DP  - 1999 Aug
TI  - SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.
PG  - 193-9
AB  - Degradation of the mammalian cyclin-dependent kinase (CDK) inhibitor p27 is
      required for the cellular transition from quiescence to the proliferative state. 
      The ubiquitination and subsequent degradation of p27 depend on its
      phosphorylation by cyclin-CDK complexes. However, the ubiquitin-protein ligase
      necessary for p27 ubiquitination has not been identified. Here we show that the
      F-box protein SKP2 specifically recognizes p27 in a phosphorylation-dependent
      manner that is characteristic of an F-box-protein-substrate interaction.
      Furthermore, both in vivo and in vitro, SKP2 is a rate-limiting component of the 
      machinery that ubiquitinates and degrades phosphorylated p27. Thus, p27
      degradation is subject to dual control by the accumulation of both SKP2 and
      cyclins following mitogenic stimulation.
FAU - Carrano, A C
AU  - Carrano AC
AD  - Department of Pathology, New York University Medical Center, New York 10016, USA.
FAU - Eytan, E
AU  - Eytan E
FAU - Hershko, A
AU  - Hershko A
FAU - Pagano, M
AU  - Pagano M
LA  - eng
GR  - R01 CA76584/CA/NCI NIH HHS/United States
GR  - R01 GM57587/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  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Oligodeoxyribonucleotides, Antisense)
RN  - 0 (RNA, Messenger)
RN  - 0 (S-Phase Kinase-Associated Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (Ubiquitins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Base Sequence
MH  - Cell Cycle Proteins/genetics/*metabolism
MH  - Cell Line
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - Cyclin-Dependent Kinases/*antagonists & inhibitors
MH  - Enzyme Inhibitors/*metabolism
MH  - HeLa Cells
MH  - Humans
MH  - In Vitro Techniques
MH  - Kinetics
MH  - Microtubule-Associated Proteins/*metabolism
MH  - Oligodeoxyribonucleotides, Antisense/genetics/pharmacology
MH  - Phosphorylation
MH  - Protein Binding
MH  - RNA, Messenger/genetics/metabolism
MH  - S-Phase Kinase-Associated Proteins
MH  - *Tumor Suppressor Proteins
MH  - Ubiquitins/*metabolism
EDAT- 1999/11/13 00:00
MHDA- 1999/11/13 00:01
CRDT- 1999/11/13 00:00
PHST- 1999/11/13 00:00 [pubmed]
PHST- 1999/11/13 00:01 [medline]
PHST- 1999/11/13 00:00 [entrez]
AID - 10.1038/12013 [doi]
PST - ppublish
SO  - Nat Cell Biol. 1999 Aug;1(4):193-9. doi: 10.1038/12013.