Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb

Cancer Cell. 2002 Nov;2(5):387-99. doi: 10.1016/s1535-6108(02)00182-4.

Tiziana Bruno ¹, Roberta De Angelis, Francesca De Nicola, Christian Barbato, Monica Di Padova, Nicoletta Corbi, Valentina Libri, Barbara Benassi, Elisabetta Mattei, Alberto Chersi, Silvia Soddu, Aristide Floridi, Claudio Passananti, Maurizio Fanciulli

Affiliations

Affiliation

1 Laboratory B, Via delle Messi d'Oro 156, 00158 Rome, Italy.

PMID: 12450794 DOI: 10.1016/s1535-6108(02)00182-4

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.

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