|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 49, 48805-48814, December 5, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Smad4 and 
-Catenin Co-activators Functionally Interact with Lymphoid-enhancing Factor to Regulate Graded Expression of Msx2*
From the Brain Tumor Research Center, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada
Recent in vivo evidence suggests that Wnt signaling plays a central role in determining the fate of stem cells in the ectoderm and in the neural crest by modulating bone morphogenetic protein (BMP) levels, which, in turn, influence Msx gene expression. However, the molecular mechanism regulating the expression of the Msx genes as key regulators of cell fate has not been elucidated. Here we show in murine embryonic stem cells that BMP-dependent activation of Msx2 is mediated via the cooperative binding of Smad4 at two Smad binding elements and of lymphoid enhancing factor (Lef1) at two Lef1/TCF binding sites. Lef1 can synergize with Smad4 and Smad1 to activate Msx2 promoter, and this transcriptional complex is assembled on the endogenous promoter in response to BMP2. The Wnt/
-catenin signaling pathway can activate Msx2 via the binding of Lef1 to its promoter and synergizes with BMP2 to activate Msx2 expression, possibly via enhanced recruitment of the p300/cAMP-response element-binding protein-binding protein co-factor. Interestingly, the Wnt/-catenin-dependent activation of Msx2 was defective in Smad4-deficient embryonic stem cells or when Smad binding elements were mutated but persisted in the presence of various BMP antagonists, indicating that Smad4 was involved in transducing the Wnt/-catenin signals in the absence of a BMP autocrine loop. A chromatin immunoprecipitation analysis revealed that endogenous Smad4, but not Smad1, was part of the Lef1 transcriptional complex in response to -catenin activation, dismissing any implication of BMP signaling in this response. We propose that Wnt signaling pathway could dictate cell fate not only by modulating BMP levels but also by directly regulating cooperatively BMP-target genes.
Received for publication, May 24, 2003 , and in revised form, October 3, 2003.
* This work was supported in part by the National Cancer Institute of Canada with funds from the Terry Fox Run. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Research Scientist of the National Cancer Institute of Canada with funds provided by the Canadian Cancer Society. To whom correspondence should be addressed: 3801 University St., Montreal, QC H3A 2B4, Canada. Tel.: 514-398-7329; Fax: 514-398-6547; E-mail: christian.sirard{at}mcgill.ca.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Patthey, T. Edlund, and L. Gunhaga Wnt-regulated temporal control of BMP exposure directs the choice between neural plate border and epidermal fate Development, January 1, 2009; 136(1): 73 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ambrosetti, G. Holmes, A. Mansukhani, and C. Basilico Fibroblast Growth Factor Signaling Uses Multiple Mechanisms To Inhibit Wnt-Induced Transcription in Osteoblasts Mol. Cell. Biol., August 1, 2008; 28(15): 4759 - 4771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Romero, M. Iglesias, C. P.H. Vary, and M. Quintanilla Functional blockade of Smad4 leads to a decrease in {beta}-catenin levels and signaling activity in human pancreatic carcinoma cells Carcinogenesis, May 1, 2008; 29(5): 1070 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Satoh, S. Hamada, K. Kimura, A. Kanno, M. Hirota, J. Umino, W. Fujibuchi, A. Masamune, N. Tanaka, K. Miura, et al. Up-Regulation of MSX2 Enhances the Malignant Phenotype and Is Associated with Twist 1 Expression in Human Pancreatic Cancer Cells Am. J. Pathol., April 1, 2008; 172(4): 926 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Amen, X. Liu, U. Vadlamudi, G. Elizondo, E. Diamond, J. F. Engelhardt, and B. A. Amendt PITX2 and {beta}-Catenin Interactions Regulate Lef-1 Isoform Expression Mol. Cell. Biol., November 1, 2007; 27(21): 7560 - 7573. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-F. Dong, D. Y. Soung, Y. Chang, M. Enomoto-Iwamoto, M. Paris, R. J. O'Keefe, E. M. Schwarz, and H. Drissi Transforming Growth Factor-{beta} and Wnt Signals Regulate Chondrocyte Differentiation through Twist1 in a Stage-Specific Manner Mol. Endocrinol., November 1, 2007; 21(11): 2805 - 2820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Brugmann, L. H. Goodnough, A. Gregorieff, P. Leucht, D. ten Berge, C. Fuerer, H. Clevers, R. Nusse, and J. A. Helms Wnt signaling mediates regional specification in the vertebrate face Development, September 15, 2007; 134(18): 3283 - 3295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hayashi, R. C. Burghardt, F. W. Bazer, and T. E. Spencer WNTs in the Ovine Uterus: Potential Regulation of Periimplantation Ovine Conceptus Development Endocrinology, July 1, 2007; 148(7): 3496 - 3506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Hens, P. Dann, J.-P. Zhang, S. Harris, G. W. Robinson, and J. Wysolmerski BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction Development, March 15, 2007; 134(6): 1221 - 1230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-R. Shiou, A. B. Singh, K. Moorthy, P. K. Datta, M. K. Washington, R. D. Beauchamp, and P. Dhawan Smad4 Regulates Claudin-1 Expression in a Transforming Growth Factor-{beta}-Independent Manner in Colon Cancer Cells Cancer Res., February 15, 2007; 67(4): 1571 - 1579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Labbe, L. Lock, A. Letamendia, A. E. Gorska, R. Gryfe, S. Gallinger, H. L. Moses, and L. Attisano Transcriptional Cooperation between the Transforming Growth Factor-{beta} and Wnt Pathways in Mammary and Intestinal Tumorigenesis Cancer Res., January 1, 2007; 67(1): 75 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hayashi, S. Nakamura, W. Nishida, and K. Sobue Bone Morphogenetic Protein-Induced Msx1 and Msx2 Inhibit Myocardin-Dependent Smooth Muscle Gene Transcription Mol. Cell. Biol., December 15, 2006; 26(24): 9456 - 9470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Blank, G. Karlsson, J. L. Moody, T. Utsugisawa, M. Magnusson, S. Singbrant, J. Larsson, and S. Karlsson Smad7 promotes self-renewal of hematopoietic stem cells Blood, December 15, 2006; 108(13): 4246 - 4254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Lim and F. M. Hoffmann Smad4 cooperates with lymphoid enhancer-binding factor 1/T cell-specific factor to increase c-myc expression in the absence of TGF-beta signaling PNAS, December 5, 2006; 103(49): 18580 - 18585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Diamond, M. Amen, Q. Hu, H. M. Espinoza, and B. A. Amendt Functional interactions between Dlx2 and lymphoid enhancer factor regulate Msx2 Nucleic Acids Res., November 6, 2006; 34(20): 5951 - 5965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hayashi and T. E. Spencer WNT Pathways in the Neonatal Ovine Uterus: Potential Specification of Endometrial Gland Morphogenesis by SFRP2 Biol Reprod, April 1, 2006; 74(4): 721 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ishii, J. Han, H.-Y. Yen, H. M. Sucov, Y. Chai, and R. E. Maxson Jr Combined deficiencies of Msx1 and Msx2 cause impaired patterning and survival of the cranial neural crest Development, November 15, 2005; 132(22): 4937 - 4950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nakashima, T. Katagiri, and M. Tamura Cross-talk between Wnt and Bone Morphogenetic Protein 2 (BMP-2) Signaling in Differentiation Pathway of C2C12 Myoblasts J. Biol. Chem., November 11, 2005; 280(45): 37660 - 37668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Osyczka and P. S. Leboy Bone Morphogenetic Protein Regulation of Early Osteoblast Genes in Human Marrow Stromal Cells Is Mediated by Extracellular Signal-Regulated Kinase and Phosphatidylinositol 3-Kinase Signaling Endocrinology, August 1, 2005; 146(8): 3428 - 3437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lyu and C.-K. Joo Wnt-7a Up-regulates Matrix Metalloproteinase-12 Expression and Promotes Cell Proliferation in Corneal Epithelial Cells during Wound Healing J. Biol. Chem., June 3, 2005; 280(22): 21653 - 21660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Masaki, M. Izumi, Y. Oshima, Y. Nakaoka, T. Kuroda, R. Kimura, S. Sugiyama, K. Terai, M. Kitakaze, K. Yamauchi-Takihara, et al. Smad1 Protects Cardiomyocytes From Ischemia-Reperfusion Injury Circulation, May 31, 2005; 111(21): 2752 - 2759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kleber, H.-Y. Lee, H. Wurdak, J. Buchstaller, M. M. Riccomagno, L. M. Ittner, U. Suter, D. J. Epstein, and L. Sommer Neural crest stem cell maintenance by combinatorial Wnt and BMP signaling J. Cell Biol., April 25, 2005; 169(2): 309 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-M. I. Yu, B. Jerchow, T.-J. Sheu, B. Liu, F. Costantini, J. E. Puzas, W. Birchmeier, and W. Hsu The role of Axin2 in calvarial morphogenesis and craniosynostosis Development, April 15, 2005; 132(8): 1995 - 2005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-C. Chang, D.-Y. Lin, H.-I Fang, R.-H. Chen, and H.-M. Shih Daxx Mediates the Small Ubiquitin-like Modifier-dependent Transcriptional Repression of Smad4 J. Biol. Chem., March 18, 2005; 280(11): 10164 - 10173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Hu and N. D. Rosenblum Smad1, {beta}-catenin and Tcf4 associate in a molecular complex with the Myc promoter in dysplastic renal tissue and cooperate to control Myc transcription Development, January 1, 2005; 132(1): 215 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Daniels, K. Shimizu, A. M. Zorn, and S.-i. Ohnuma Negative regulation of Smad2 by PIASy is required for proper Xenopus mesoderm formation Development, November 15, 2004; 131(22): 5613 - 5626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Brugger, A. E. Merrill, J. Torres-Vazquez, N. Wu, M.-C. Ting, J. Y.-M. Cho, S. L. Dobias, S. E. Yi, K. Lyons, J. R. Bell, et al. A phylogenetically conserved cis-regulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryos Development, October 15, 2004; 131(20): 5153 - 5165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lei, A. Dubeykovskiy, A. Chakladar, L. Wojtukiewicz, and T. C. Wang The Murine Gastrin Promoter Is Synergistically Activated by Transforming Growth Factor-{beta}/Smad and Wnt Signaling Pathways J. Biol. Chem., October 8, 2004; 279(41): 42492 - 42502. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |