Synergistic Cooperation between the β-Catenin Signaling Pathway and Steroidogenic Factor 1 in the Activation of the Mullerian Inhibiting Substance Type II Receptor

Anwar Hossain,Grady F Saunders

doi:10.1074/jbc.m300804200

Abstract

Mullerian inhibiting substance type II receptor (MISRII) is a member of the transforming growth factor-beta 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 regulated MISRII. The promoter MISRII was activated by beta-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 beta-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 beta-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.

Highlights

The Wnt molecules are a large family of secreted glycoproteins that play an important role in the developmental program in many organisms [12]
MISRII Promoter a Direct Target of the Wnt Signaling Pathway—To determine whether ␤-catenin and TCF4, the intracellular mediators of the Wnt signaling pathway, can activate a luciferase reporter gene driven by the MISRII promoter, we transfected Ϫ800MISRPLuc into HeLa cells
We found no evidence for a direct interaction between steroidogenic factor 1 (SF1) and TCF4 by cotransfection or by mixing in vitro translated proteins followed by IP and immunoblotting

Summary

Introduction

The Wnt molecules are a large family of secreted glycoproteins that play an important role in the developmental program in many organisms [12]. The promoter MISRII was activated by ␤-catenin expression, and this activation was dependent on TCF4-binding sites. APC, a negative regulator of Wnt signaling, decreased SF1-mediated activation of the MISRII promoter in the colon carcinoma cell line SW480.

Results

Conclusion