Author/Authors :
Bruno، نويسنده , , Tiziana and De Angelis، نويسنده , , Roberta and De Nicola، نويسنده , , Francesca and Barbato، نويسنده , , Christian and Di Padova، نويسنده , , Monica and Corbi، نويسنده , , Nicoletta and Libri، نويسنده , , Valentina and Benassi، نويسنده , , Barbara and Mattei، نويسنده , , Elisabetta and Chersi، نويسنده , , Alberto and Soddu، نويسنده , , Silvia and Floridi، نويسنده , , Aristide and Passananti، نويسنده , , Claudio and Fanciulli، نويسنده , , Maurizio، نويسنده ,
Abstract :
DNA tumor virus oncoproteins bind and inactivate Rb by interfering with the Rb/HDAC1 interaction. Che-1 is a recently identified human Rb binding protein that inhibits the Rb growth suppressing function. Here we show that Che-1 contacts the Rb pocket region and competes with HDAC1 for Rb binding site, removing HDAC1 from the Rb/E2F complex in vitro and from the E2F target promoters in vivo. Che-1 overexpression activates DNA synthesis in quiescent NIH-3T3 cells through HDAC1 displacement. Consistently, Che-1-specific RNA interference affects E2F activity and cell proliferation in human fibroblasts but not in the pocket protein-defective 293 cells. These findings indicate the existence of a pathway of Rb regulation supporting Che-1 as the cellular counterpart of DNA tumor virus oncoproteins.
