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

One class of the nuclear receptor AF-2 coactivator complexes contains the S RC-1/TIF2 family, CBP/p300 and an RNA coactivator, SRA. We identified a sub family of RNA-binding DEAD-box proteins (p72/p68) as a human estrogen recep tor alpha (hER alpha) coactivator in the complex containing these factors, p72/p68 interacted with both the AD2 of any SRC-1/TIF2 family protein and t he hER alpha A/B domain, but not with any other nuclear receptor tested. p7 2/p68, TIF2 (SRC-1) and SRA were co-immunoprecipitated with estrogen-bound hER alpha in MCF7 cells and in partially purified complexes associated with hER alpha from HeLa nuclear extracts. Estrogen induced co-localization of p72 with hER alpha and TIF2 in the nucleus. The presence of p72/ p68 potent iated the estrogen-induced expression of the endogenous pS2 gene in MCF7 ce lls. In a transient expression assay, a combination of p72/p68 with SRA and one TIF2, brought an ultimate synergism to the estrogen-induced transactiv ation of hER alpha. These findings indicate that p72/p68 acts as an ER subt ype-selective coactivator through ER alpha AF-1 by associating with the coa ctivator complex to bind its AF-2 through direct binding with SRA and the S RC-1/TIF2 family proteins.