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

TY - JOUR

T1 - p27KIP1 blocks cyclin E-dependent transactivation of cyclin A gene expression.

AU - Zerfass-Thome, K

AU - Schulze, A

AU - Zwerschke, W

AU - Vogt, B

AU - Helin, K

AU - Bartek, J

AU - Henglein, B

AU - Jansen-Dürr, P

N1 - Keywords: 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; Cyclins; DNA-Binding Proteins; E2F Transcription Factors; Enzyme Inhibitors; G1 Phase; Humans; Mice; Microtubule-Associated Proteins; Models, Genetic; Nuclear Proteins; Promoter Regions (Genetics); Protein Binding; Protein-Serine-Threonine Kinases; Recombinant Fusion Proteins; Retinoblastoma-Like Protein p107; Trans-Activation (Genetics); Transcription Factor DP1; Transcription Factors; Transfection; Tumor Suppressor Proteins

PY - 1997

Y1 - 1997

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 8972221

SN - 0270-7306

VL - 17

SP - 407

EP - 415

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

IS - 1

ER -