A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites.

Abstract:

:An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F and for RB to induce a G1/S block. Indirect evidence suggests that the binding of RB to E2F may, in addition to inhibiting E2F transactivation function, generate a complex capable of functioning as a transrepressor. Here we show that a chimera in which the E2F1 transactivation domain was replaced with the RB pocket could, in a DNA-binding and pocket-dependent manner, mimic the ability of RB to repress transcription and induce a cell cycle arrest. In contrast, a transdominant negative E2F1 mutant that is capable of blocking E2F-dependent transactivation did not. Fusion of the RB pocket to a heterologous DNA-binding domain unrelated to E2F likewise generated a transrepressor protein when scored against a suitable reporter. These results suggest that growth suppression by RB is due, at least in part, to transrepression mediated by the pocket domain bound to certain promoters via E2F.

authors

Sellers WR,Rodgers JW,Kaelin WG Jr

doi

10.1073/pnas.92.25.11544

subject

Has Abstract

pub_date

1995-12-05 00:00:00

pages

11544-8

issue

25

eissn

0027-8424

issn

1091-6490

journal_volume

92

pub_type

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