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PMID: 8033213 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21.

Cell ·Vol. 78 ·No. 1 ·1994-07-15 ·Pages 67-74

Toyoshima H, Hunter T

Abstract

Using a yeast interaction screen to search for proteins that interact with cyclin D1-Cdk4, we identified a 27 kDa mouse protein related to the p21 cyclin-Cdk inhibitor. p27 interacts strongly with D-type cyclins and Cdk4 in vitro and more weakly with cyclin E and Cdk2. In mouse fibroblasts, p27 is associated predominantly with cyclin D1-Cdk4. Recombinant p27 is a potent inhibitor of cyclin D1-Cdk4 and cyclin A-Cdk2 protein kinase activity and a weaker inhibitor of cyclin B1-Cdc2. Overexpression of p27 in Saos-2 cells causes G1 arrest. p27 protein levels do not change as serum-stimulated quiescent mouse fibroblasts progress through the cell cycle. p27 is identical to p27Kip1, a cyclin-Cdk inhibitor present in TGF beta-treated cells. p27 has the hallmarks of a negative regulator of G1 progression and may mediate TGF beta-induced G1 arrest.

MeSH Terms
3T3 Cells Amino Acid Sequence Animals Base Sequence CDC2-CDC28 Kinases Cell Cycle/drug effects Cell Cycle Proteins Cell Line Cloning, Molecular Cyclin D1 Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases Cyclins/genetics,metabolism Fungal Proteins/genetics,metabolism,pharmacology G1 Phase/drug effects Gene Expression Regulation Mice Microtubule-Associated Proteins/genetics,metabolism,pharmacology Molecular Sequence Data Oncogene Proteins/genetics,metabolism Open Reading Frames Protein Kinase Inhibitors Protein Serine-Threonine Kinases Proto-Oncogene Proteins RNA, Messenger/analysis Recombinant Fusion Proteins/metabolism Sequence Analysis, DNA Tumor Suppressor Proteins Yeasts/metabolism
Chemicals
Cdkn1b protein, mouse Cell Cycle Proteins Cyclins Fungal Proteins Microtubule-Associated Proteins Oncogene Proteins Protein Kinase Inhibitors Proto-Oncogene Proteins RNA, Messenger Recombinant Fusion Proteins Tumor Suppressor Proteins Cyclin D1 Cyclin-Dependent Kinase Inhibitor p27 Protein Serine-Threonine Kinases CDC2-CDC28 Kinases Cdk2 protein, mouse Cdk4 protein, mouse Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Toyoshima H
Molecular Biology and Virology Laboratory, Salk Institute, La Jolla, California 92037.
Hunter T
Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/0092-8674(94)90573-8
Published
1994-07-15
Pages
67-74
Language
English
Region
United States
NLM ID
0413066
Subset
IM
Grants
NCI NIH HHS · CA14195 · United States
NCI NIH HHS · CA39780 · United States
Databases
GENBANK
U10440
External Links
PubMed source DOI: 10.1016/0092-8674(94)90573-8 View journal details
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