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PMID: 8756619 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Anchorage-dependent transcription of the cyclin A gene.

Molecular and cellular biology ·Vol. 16 ·No. 9 ·1996-09-00 ·Pages 4632-8

Schulze A, Zerfass-Thome K, Bergès J, Middendorp S, Jansen-Dürr P, Henglein B

Abstract

NIH 3T3 cells cultured in suspension fail to express cyclin A and hence cannot enter S phase and divide. We show that loss of cell adhesion to substratum abrogates cyclin A gene expression by blocking its promoter activity through the E2F site that mediates its cell cycle regulation in adherent cells. In suspended cells, G0-specific E2F complexes remain bound to the cyclin A promoter. Overexpression of cyclin D1 restores cyclin A transcription in suspended cells and rescues them from cell cycle arrest. In suspended cells, cyclin D1 and cyclin E accumulate normally upon serum stimulation, but their associated kinases remain inactive; their substrates, pRb and p107, are not hyperphosphorylated. Concomitantly, the cyclin-dependent kinase inhibitor, p27KIP1, is stabilized. Ectopic expression of p27KIP1 blocks cyclin A promoter activity through its EN binding site. These data suggest that the block to cyclin A transcription in nonadherent NIH 3T3 cells results from stabilization of p27KIP1 and subsequent inactivation of the specific E2F moiety required for its induction.

MeSH Terms
3T3 Cells Animals Base Sequence Carrier Proteins Cell Adhesion/physiology Cell Cycle Proteins Cyclin D1 Cyclin-Dependent Kinase Inhibitor p27 Cyclins/biosynthesis,genetics,physiology DNA-Binding Proteins E2F Transcription Factors Gene Expression Regulation Mice Microtubule-Associated Proteins/physiology Molecular Sequence Data Oncogene Proteins/genetics,physiology Promoter Regions, Genetic Recombinant Fusion Proteins/biosynthesis Resting Phase, Cell Cycle/genetics Retinoblastoma-Binding Protein 1 Transcription Factor DP1 Transcription Factors/physiology Transcription, Genetic Tumor Suppressor Proteins
Chemicals
Arid4a protein, mouse Carrier Proteins Cdkn1b protein, mouse Cell Cycle Proteins Cyclins DNA-Binding Proteins E2F Transcription Factors Microtubule-Associated Proteins Oncogene Proteins Recombinant Fusion Proteins Retinoblastoma-Binding Protein 1 Transcription Factor DP1 Transcription Factors Tumor Suppressor Proteins Cyclin D1 Cyclin-Dependent Kinase Inhibitor p27
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Schulze A
Forschungschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Zerfass-Thome K
Bergès J
Middendorp S
Jansen-Dürr P
Henglein B
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.16.9.4632
Published
1996-09-00
Pages
4632-8
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231462
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.16.9.4632 PMC Full Text View journal details
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