NEGATIVE REGULATION OF THE GROWTH-PROMOTING TRANSCRIPTION FACTOR E2F-1 BY A STABLY BOUND CYCLIN A-DEPENDENT PROTEIN-KINASE

Cyclin A-kinase, an enzyme required for coordinating S phase progressi on, forms stable in vivo complexes with E2F-1, a growth-promoting tran scription factor, which binds to the retinoblastoma gene product and i s involved in the timely activation of genes whose products contribute to G1 exit and S phase traversal. Complex formation results in a nega tive biochemical effect of cyclin A-kinase: the shut-off of E2F-1-depe ndent DNA binding function in S/G2. Thus, specific and timely cell cyc le-dependent interactions of E2F-1 with proteins that inhibit its func tion (i.e., RB during G1 and cyclin A-kinase during S/G2) may contribu te to the periodicity of expression of certain E2F-1-responsive genes at the G1/S transition.