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Mol. Cell. Biol., Sep 1996, 4632-4638, Vol 16, No. 9
A Schulze, K Zerfass-Thome, J Berges, S Middendorp, P Jansen-Durr and B Henglein
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.
Copyright © 1996, American Society for Microbiology
Anchorage-dependent transcription of the cyclin A gene
Forschungschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
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