Negative regulation of the growth-promoting transcription factor E2F-1 by a stably bound cyclin A-dependent protein kinase

W Krek, ME Ewen, S Shirodkar, Z Arany, WG Kaelin Jr… - Cell, 1994 - cell.com
W Krek, ME Ewen, S Shirodkar, Z Arany, WG Kaelin Jr, DM Livingston
Cell, 1994cell.com
Cyclin A-kinase, an enzyme required for coordinating S phase progression, forms stable in
vivo complexes with E2F-1, a growth-promoting transcription factor, which binds to the
retinoblastoma gene product and is involved in the timely activation of genes whose
products contribute to Gl exit and S phase traversal. Complex formation results in a negative
biochemical effect of cyclin A-kinase: the shut-off of ESF-l-dependent DNA binding function
in S/G2. Thus, specific and timely cell cycle-dependent interactions of E2F-1 with proteins …
Summary
Cyclin A-kinase, an enzyme required for coordinating S phase progression, forms stable in vivo complexes with E2F-1, a growth-promoting transcription factor, which binds to the retinoblastoma gene product and is involved in the timely activation of genes whose products contribute to Gl exit and S phase traversal. Complex formation results in a negative biochemical effect of cyclin A-kinase: the shut-off of ESF-l-dependent DNA binding function in S/G2. Thus, specific and timely cell cycle-dependent interactions of E2F-1 with proteins that inhibit its function (ie, RB during Gl and cyclin A-kinase during SIG2) may contribute to the perlodicity of expression of certain EPF-l-responsive genes at the GllS transition.
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