pRB binds to and modulates the transrepressing activity of the E1A-regulated transcription factor p120(E4F)

The retinoblastoma protein pRB is involved in the transcriptional control o f genes essential for cell cycle progression and differentiation, pRB inter acts with different transcription factors and thereby modulates their activ ity by sequestration, corepression, or activation. We report that pRB, but not p107 and p130, binds to and facilitates repression by p120(E4F), a ubiq uitously expressed GLI-Kruppel-related protein identified as a cellular tar get of E1A. The interaction involves two distinct regions of p120(E4F) and the C-terminal part of pRB. In vivo pRB-p120(E4F) complexes can only be det ected in growth-arrested cells, and accordingly contain the hypophosphoryla ted form of pRB. Repression of an E4F-responsive promoter is strongly incre ased by combined expression of p120(E4F) and pRB, which correlates with pRB -dependent enhancement of p120(E4F) binding activity. Elevated levels of p1 20(E4F) have been shown to block growth of mouse fibroblasts in G(1). We fi nd this requires pRB, because RB-/- fibroblasts are significantly less sens itive to excess p120(E4F).