Synergistic Cooperation between the β-Catenin Signaling Pathway and Steroidogenic Factor 1 in the Activation of the Mullerian Inhibiting Substance Type II Receptor
Journal of Biological Chemistry
Mullerian inhibiting substance type II receptor (MISRII) is a member of the transforming growth factor-␤ superfamily. Mutations in mullerian inhibiting substance (MIS) or MISRII cause male sexual abnormalities, persistent mullerian duct syndrome, and pseudohermaphroditism. The spatial and temporal regulation of MIS and MISRII is important for its biological action. Male Wnt7a mutant mice do not undergo regression of mullerian ducts. Here we showed that the canonical Wnt signaling pathway
... ling pathway regulated MISRII. The promoter MISRII was activated by ␤-catenin expression, and this activation was dependent on TCF4-binding sites. The nuclear receptor superfamily member steroidogenic factor 1 (SF1) synergistically activated the MISRII promoter with ␤-catenin. APC, a negative regulator of Wnt signaling, decreased SF1-mediated activation of the MISRII promoter in the colon carcinoma cell line SW480. We also showed a direct physical interaction between ␤-catenin and SF1 by co-immunoprecipitation. Thus, our findings suggest that MISRII is a developmental target of Wnt7a signaling for mullerian duct regression during sexual differentiation.