PRB AND P107 P130 ARE REQUIRED FOR THE REGULATED EXPRESSION OF DIFFERENT SETS OF E2F RESPONSIVE GENES/

The activity of the E2F transcription factor is controlled by physical association with the retinoblastoma protein (pRB) and two related pro teins, p107 and p130. The pRB family members are thought to control di fferent aspects of E2F activity, but it has been unclear what the resp ective functions of these proteins might be. To dissect the specific f unctions of pRB, p107, and p130 we have investigated how the expressio n of E2F-regulated genes is changed in cultures of primary cells lacki ng each of these family members. Whereas no changes were found in the expression of E2F-target genes in cells lacking either p107 or p130, d eregulated expression of E2F targets was seen in cells lacking pRB and in cells lacking both p107 and p130. Surprisingly, the genes that wer e disregulated in these two settings were completely different. These findings show that PRE and p107/p130 indeed provide different function s in E2F regulation and identify target genes that are dependent on pR B family proteins for their normal expression.