WW-domain binding protein-2 (WBP-2) was cloned as an E6-associated protein (E6-AP) interacting protein and its role in steroid hormone receptors functions was investigated. We show that WBP-2 specifically enhanced the transactivation functions of progesterone receptor (PR) and estrogen receptor (ER), whereas it did not have any significant effect on the androgen receptor, glucocorticoid receptor or the activation functions of p53 and VP-16. Depletion of endogenous WBP-2 with small interfering RNAs indicated that WBP-2 was required for the proper functioning of PR and ER. We also demonstrated that WBP-2 contains an intrinsic activation domain. Moreover, chromatin immunoprecipitation assays demonstrate the hormone-dependent recruitment of WBP-2 onto an estrogen-responsive promoter. Mutational analysis suggests that one of three polyproline (PY) motifs of WBP-2 is essential for its coactivation and intrinsic activation functions. We show that WBP-2 and E6-AP each enhance PR function and their effect on PR action are additive when coexpressed suggesting a common signaling pathway. In this study, we also demonstrate that the WBP-2 binding protein, Yes-kinase associated protein (YAP) enhances PR transactivation but YAP's coactivation function is absolutely dependent on WBP-2. Taken together our data establish the role of WBP-2 and YAP as coactivators for ER and PR transactivation pathways.