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PMID: 8972221 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

p27KIP1 blocks cyclin E-dependent transactivation of cyclin A gene expression.

Molecular and cellular biology ·Vol. 17 ·No. 1 ·1997-01-00 ·Pages 407-15

Zerfass-Thome K, Schulze A, Zwerschke W, Vogt B, Helin K, Bartek J, Henglein B, Jansen-Dürr P

Abstract

Cyclin E is necessary and rate limiting for the passage of mammalian cells through the G1 phase of the cell cycle. Control of cell cycle progression by cyclin E involves cdk2 kinase, which requires cyclin E for catalytic activity. Expression of cyclin E/cdk2 leads to an activation of cyclin A gene expression, as monitored by reporter gene constructs derived from the human cyclin A promoter. Promoter activation by cyclin E/cdk2 requires an E2F binding site in the cyclin A promoter. We show here that cyclin E/cdk2 kinase can directly bind to E2F/p107 complexes formed on the cyclin A promoter-derived E2F binding site, and this association is controlled by p27KIP1, most likely through direct protein-protein interaction. These observation suggest that cyclin E/cdk2 associates with E2F/p107 complexes in late G1 phase, once p27KIP1 has decreased below a critical threshold level. Since a kinase-negative mutant of cdk2 prevents promoter activation, it appears that transcriptional activation of the cyclin A gene requires an active cdk2 kinase tethered to its promoter region.

MeSH Terms
3T3 Cells Animals Binding Sites CDC2-CDC28 Kinases Carrier Proteins Cell Cycle Proteins Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases/antagonists & inhibitors,genetics,metabolism Cyclins/genetics,metabolism DNA-Binding Proteins E2F Transcription Factors Enzyme Inhibitors G1 Phase/physiology Humans Mice Microtubule-Associated Proteins/analysis,physiology Models, Genetic Nuclear Proteins/genetics,metabolism Promoter Regions, Genetic/genetics Protein Binding Protein Serine-Threonine Kinases/antagonists & inhibitors,genetics,metabolism Recombinant Fusion Proteins Retinoblastoma-Binding Protein 1 Retinoblastoma-Like Protein p107 Transcription Factor DP1 Transcription Factors/metabolism Transcriptional Activation/physiology Transfection Tumor Suppressor Proteins
Chemicals
Arid4a protein, mouse Carrier Proteins Cdkn1b protein, mouse Cell Cycle Proteins Cyclins DNA-Binding Proteins E2F Transcription Factors Enzyme Inhibitors Microtubule-Associated Proteins Nuclear Proteins RBL1 protein, human Rbl1 protein, mouse Recombinant Fusion Proteins Retinoblastoma-Binding Protein 1 Retinoblastoma-Like Protein p107 Transcription Factor DP1 Transcription Factors Tumor Suppressor Proteins Cyclin-Dependent Kinase Inhibitor p27 Protein Serine-Threonine Kinases CDC2-CDC28 Kinases CDK2 protein, human Cdk2 protein, mouse Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Zerfass-Thome K
Forschungsschwerpunkt Angewandte Tumorvirologie, Abteilung 620, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Schulze A
Zwerschke W
Vogt B
Helin K
Bartek J
Henglein B
Jansen-Dürr P
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.17.1.407
Published
1997-01-00
Pages
407-15
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231765
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.17.1.407 PMC Full Text View journal details
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