PMID- 10086358
OWN - NLM
STAT- MEDLINE
DCOM- 19990329
LR  - 20171116
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 398
IP  - 6723
DP  - 1999 Mar 11
TI  - Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by
      Jab1.
PG  - 160-5
AB  - The proliferation of mammalian cells is under strict control, and the
      cyclin-dependent-kinase inhibitory protein p27Kip1 is an essential participant in
      this regulation both in vitro and in vivo. Although mutations in p27Kip1 are
      rarely found in human tumours, reduced expression of the protein correlates well 
      with poor survival among patients with breast or colorectal carcinomas,
      suggesting that disruption of the p27Kip1 regulatory mechanisms contributes to
      neoplasia. The abundance of p27Kip1 in the cell is determined either at or after 
      translation, for example as a result of phosphorylation by cyclinE/Cdk2
      complexes, degradation by the ubiquitin/proteasome pathway, sequestration by
      unknown Myc-inducible proteins, binding to cyclinD/Cdk4 complexes, or
      inactivation by the viral E1A oncoprotein. We have found that a mouse 38K protein
      (p38) encoded by the Jab1 gene interacts specifically with p27Kip1 and show here 
      that overexpression of p38 in mammalian cells causes the translocation of p27Kip1
      from the nucleus to the cytoplasm, decreasing the amount of p27Kip1 in the cell
      by accelerating its degradation. Ectopic expression of p38 in mouse fibroblasts
      partially overcomes p27Kip1-mediated arrest in the G1 phase of the cell cycle and
      markedly reduces their dependence on serum. Our findings indicate that p38
      functions as a negative regulator of p27Kip1 by promoting its degradation.
FAU - Tomoda, K
AU  - Tomoda K
AD  - Graduate School of Biological Sciences, Nara Institute of Science and Technology,
      Ikoma, Japan.
FAU - Kubota, Y
AU  - Kubota Y
FAU - Kato, J
AU  - Kato J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Cdkn1b protein, mouse)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.-.- (COPS5 protein, human)
RN  - EC 3.4.-.- (Cops5 protein, mouse)
RN  - EC 3.4.19.12 (COP9 Signalosome Complex)
SB  - IM
CIN - Nature. 1999 Mar 11;398(6723):103-4. PMID: 10086352
MH  - 3T3 Cells
MH  - Animals
MH  - COP9 Signalosome Complex
MH  - COS Cells
MH  - Cell Cycle
MH  - *Cell Cycle Proteins
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - Cyclin-Dependent Kinases/antagonists & inhibitors
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Down-Regulation
MH  - Enzyme Inhibitors/metabolism
MH  - G1 Phase
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microtubule-Associated Proteins/genetics/*metabolism
MH  - Mutagenesis
MH  - Peptide Hydrolases
MH  - Protein Binding
MH  - Recombinant Fusion Proteins/metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - *Tumor Suppressor Proteins
EDAT- 1999/03/23 03:03
MHDA- 2001/03/23 10:01
CRDT- 1999/03/23 03:03
PHST- 1999/03/23 03:03 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/03/23 03:03 [entrez]
AID - 10.1038/18230 [doi]
PST - ppublish
SO  - Nature. 1999 Mar 11;398(6723):160-5. doi: 10.1038/18230.