THE PRB-RELATED PROTEIN P130 IS A POSSIBLE EFFECTOR OF TRANSFORMING GROWTH-FACTOR-BETA-1 INDUCED CELL-CYCLE ARREST IN KERATINOCYTES

Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit epi thelial cell growth by inducing a G1 cell cycle arrest. We have studie d the effect of TGF-beta 1 on protein binding to a transcription facto r E2F consensus element in extracts from early passage human keratinoc ytes (HFKs) and a permanent human keratinocyte cell line (HaCaT). Trea tment of these cells with TGF-beta 1 resulted in the formation of a DN A binding complex between the pRb-related protein p130 and E2F. Format ion of the E2F-p130 complex correlated with inhibition of cell cycle p rogression in G1 and suppression of the E2F-regulated cdc2 gene. While p130 mRNA and protein levels were not influenced by TGF-beta 1, the a ctivity of cyclin-dependent kinase 2 (Cdk2) towards p130 in vitro was inhibited. The results identify p130 as a downstream target of TGF-bet a 1 and a possible mediator of the G1 cell cycle arrest.