A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor α coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA

Abstract

One class of the nuclear receptor AF‐2 coactivator complexes contains the SRC‐1/TIF2 family, CBP/p300 and an RNA coactivator, SRA. We identified a subfamily of RNA‐binding DEAD‐box proteins (p72/p68) as a human estrogen receptor α (hERα) coactivator in the complex containing these factors. p72/p68 interacted with both the AD2 of any SRC‐1/TIF2 family protein and the hERα A/B domain, but not with any other nuclear receptor tested. p72/p68, TIF2 (SRC‐1) and SRA were co‐immunoprecipitated with estrogen‐bound hERα in MCF7 cells and in partially purified complexes associated with hERα from HeLa nuclear extracts. Estrogen induced co‐localization of p72 with hERα and TIF2 in the nucleus. The presence of p72/p68 potentiated the estrogen‐induced expression of the endogenous pS2 gene in MCF7 cells. In a transient expression assay, a combination of p72/p68 with SRA and one TIF2 brought an ultimate synergism to the estrogen‐induced transactivation of hERα. These findings indicate that p72/p68 acts as an ER subtype‐selective coactivator through ERα AF‐1 by associating with the coactivator complex to bind its AF‐2 through direct binding with SRA and the SRC‐1/TIF2 family proteins.