INTERACTION OF D-TYPE CYCLINS WITH A NOVEL MYB-LIKE TRANSCRIPTION FACTOR, DMP1

The cyclin D-dependent kinases CDK4 and CDK6 trigger phosphorylation o f the retinoblastoma protein (RE) late in G(1) phase, helping to cance l its growth-suppressive function and thereby facilitating S-phase ent ry, Although specific inhibition of cyclin D-dependent kinase activity in vivo can prevent cells from entering S phase, it does not affect S -phase entry in cells lacking functional RE, implying that RE may be t he only substrate of CDK4 and CDK6 whose phosphorylation is necessary for G(1) exit, Using a yeast two-hybrid interactive screen, we have no w isolated a novel cyclin D-interacting myb like protein (designated D MP1), which binds specifically to the nonamer DNA consensus sequences CCCG(G/T)ATGT to activate transcription. A subset of these DMP1 recogn ition sequences containing a GGA trinucleotide core can also function as Ets-responsive elements, DMP1 mRNA and protein are ubiquitously exp ressed throughout the cell cycle in mouse tissues and in representativ e cell lines, DMP1 binds to D-type cyclins directly in vitro and when coexpressed in insect Sf9 cells, In both settings, it can be phosphory lated by cyclin D-dependent kinases, suggesting that its transcription al activity may normally be regulated through such mechanisms, These r esults raise the possibility that cyclin D-dependent kinases regulate gene expression in an RE independent manner, thereby serving to link o ther genetic programs to the cell cycle clock.