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Published online before print October 18, 2006, 10.1101/gad.1461706
GENES & DEVELOPMENT 20:2943-2948, 2006
©2006 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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Research Communication

Metastatic tumor antigen 3 is a direct corepressor of the Wnt4 pathway

Hao Zhang1,3, Rajesh R. Singh1,3, Amjad H. Talukder1,3, and Rakesh Kumar1,2,4

1 Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA; 2 Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA

Here we show that expression of MTA3 inhibits ductal branching in virgin and pregnant murine transgenic mammary glands. MTA3 also suppresses the Wnt4 pathway and, thus, these findings parallel phenotypic changes in Wnt4-null mice. MTA3 represses Wnt4 transcription and Wnt4 secretion, inhibiting Wnt-target genes in mammary epithelial cells. Accordingly, knockdown of endogenous MTA3 stimulates Wnt4 expression and Wnt cellular targets. The MTA3–NuRD (nucleosome remodeling and deacetylase) complex physically interacts with the Wnt4 chromatin in an HDAC-dependent manner, leading to suppression of the Wnt4 gene and Wnt4-dependent morphogenesis. These findings identify MTA3 as an upstream physiologic repressor of Wnt4 in mammary epithelial cells.

[Keywords: MTA3; WNT4; mammary gland; lactation]

Received June 21, 2006; revised version accepted September 6, 2006.

3 These authors contributed equally to this work.

4 Corresponding author.

E-MAIL rkumar{at}mdanderson.org; FAX (713) 745-3792

Supplemental material is available at http://www.genesdev.org.

Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1461706.


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B. Manavathi and R. Kumar
Metastasis Tumor Antigens, an Emerging Family of Multifaceted Master Coregulators
J. Biol. Chem., January 19, 2007; 282(3): 1529 - 1533.
[Abstract] [Full Text] [PDF]


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