This Article Full Text Full Text (PDF) All Versions of this Article: 21/4/963    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Salisbury, T. B. Articles by Nilson, J. H. Search for Related Content PubMed PubMed Citation Articles by Salisbury, T. B. Articles by Nilson, J. H.

Maximal Activity of the Luteinizing Hormoneß-Subunit Gene Requires ß-Catenin

School of Molecular Biosciences, Washington State University, Pullman, Washington 99164

Address all correspondence and requests for reprints to: John H. Nilson, School of Molecular Biosciences, Fulmer 639A, Washington State University, Pullman, Washington 99164-4660. E-mail: jhn{at}wsu.edu.

GnRH regulates expression of LHB via transcriptional regulation of early growth response 1 (EGR1), an immediate early gene that encodes a zinc-finger DNA-binding protein. EGR1 interacts functionally with the orphan nuclear receptor steroidogenic factor 1 (SF1) and pituitary homeobox 1, a member of the paired-like homeodomain family. The functional synergism of this tripartite interaction defines the maximal level of LHB transcription that can occur in response to GnRH. Results presented herein provide new evidence that the interaction between SF1 and EGR1 also requires ß-catenin, a transcriptional coactivator and member of the canonical Wnt signaling pathway. For instance, targeted reduction of ß-catenin attenuates activity of a GnRH-primed LHB promoter. Additional gene reporter assays indicate that overexpression of ß-catenin, or its targeted reduction by small interfering RNA, modulates activity of both SF1 and EGR1 as well as their functional interaction. ß-Catenin coimmunoprecipitates with SF1. Moreover, an SF1 mutant that lacks a ß-catenin binding domain has compromised transcriptional activity and fails to interact synergistically with EGR1. Finally, GnRH promotes ß-catenin colocalization with SF1 and EGR1 on the endogenous mouse Lhb promoter-regulatory region. Taken together, these data suggest that ß-catenin binds to SF1 and that this interaction is required for subsequent functional interaction with EGR1. Thus, these data identify ß-catenin as a new and required member of the basal transcriptional complex that allows the LHB promoter to achieve maximal activity in response to GnRH.

NURSA Molecule Pages Link:

Nuclear Receptors:   SF-1

This article has been cited by other articles:

				A. C. Kim, A. L. Reuter, M. Zubair, T. Else, K. Serecky, N. C. Bingham, G. G. Lavery, K. L. Parker, and G. D. Hammer Targeted disruption of {beta}-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex Development, August 1, 2008; 135(15): 2593 - 2602. [Abstract] [Full Text] [PDF]

				T. B. Salisbury, A. K. Binder, and J. H. Nilson Welcoming {beta}-Catenin to the Gonadotropin-Releasing Hormone Transcriptional Network in Gonadotropes Mol. Endocrinol., June 1, 2008; 22(6): 1295 - 1303. [Abstract] [Full Text] [PDF]

				P. Lamba, V. Khivansara, A. C. D'Alessio, M. M. Santos, and D. J. Bernard Paired-Like Homeodomain Transcription Factors 1 and 2 Regulate Follicle-Stimulating Hormone {beta}-Subunit Transcription through a Conserved cis-Element Endocrinology, June 1, 2008; 149(6): 3095 - 3108. [Abstract] [Full Text] [PDF]

				S. Gardner, S. Maudsley, R. P. Millar, and A. J. Pawson Nuclear Stabilization of {beta}-Catenin and Inactivation of Glycogen Synthase Kinase-3{beta} by Gonadotropin-Releasing Hormone: Targeting Wnt Signaling in the Pituitary Gonadotrope Mol. Endocrinol., December 1, 2007; 21(12): 3028 - 3038. [Abstract] [Full Text] [PDF]

				H. A Ferris, H. E Walsh, J. Stevens, P. C Fallest, and M. A Shupnik Luteinizing Hormone Beta Promoter Stimulation by Adenylyl Cyclase and Cooperation with Gonadotropin-Releasing Hormone 1 in Transgenic Mice and LBetaT2 Cells Biol Reprod, December 1, 2007; 77(6): 1073 - 1080. [Abstract] [Full Text] [PDF]