Synergistic cooperation between the beta-catenin signaling pathway and steroidogenic factor 1 in the activation of the Mullerian inhibiting substance type II receptor.
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.
Hossain
Anwar
A
Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.
Saunders
Grady F
GF
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation; D017491:Genes, APC; D006367:HeLa Cells; D018398:Homeodomain Proteins; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012733:Sex Differentiation / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D054339:Steroidogenic Factor 1; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D014981:Xenopus; D029867:Xenopus Proteins; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C515057:NR5A1 protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D054339:Steroidogenic Factor 1; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C544895:Tcf7l2 protein, mouse; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; C092778:WNT7A protein, human; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse; D029867:Xenopus Proteins; C084621:anti-Mullerian hormone receptor; D051176:beta Catenin; C515058:steroidogenic factor 1, mouse; C544896:tcf7l2 protein, Xenopus; D004247:DNA