HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 13, 8877-8887, March 31, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/13/8877    most recent M505784200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mao, C. Articles by Lee, A. S. Search for Related Content PubMed PubMed Citation Articles by Mao, C. Articles by Lee, A. S. Social Bookmarking                      What's this?

In Vivo Regulation of Grp78/BiP Transcription in the Embryonic Heart

ROLE OF THE ENDOPLASMIC RETICULUM STRESS RESPONSE ELEMENT AND GATA-4^*

Changhui Mao, Wei-Cheng Tai, Yan Bai, Coralie Poizat¹, and Amy S. Lee²

From the Department of Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center and the Institute for Genetic Medicine, Keck School of Medicine, Los Angeles, California 90089-9176

The transcriptional activation of GRP78, which controls multiple signaling pathways of the unfolded protein response, has been used extensively as an indicator for the onset of endoplasmic reticulum stress in tissue culture systems. Here we investigate the mechanism of Grp78 induction during mouse embryonic development. Our results reveal that in transgenic mouse models, reporter gene activity driven by the Grp78 promoter is strongly activated during early embryonic heart development but subsides in later stages. This activation is strictly dependent on a 100-base pair region of the Grp78 promoter containing the endoplasmic reticulum stress response elements (ERSEs). Previous studies establish that endoplasmic reticulum stress induces in vivo binding of YY1 and the nuclear form of ATF6 to the ERSE. Since the expression of YY1 as well as ATF6 is ubiquitous in the mouse embryo, activation of the Grp78 promoter in the early embryonic heart may involve a specific mechanism. Here we report that GATA-4, a transcription factor essential for heart development, binds to the Grp78 promoter in vivo and activates the ERSE, which does not contain a consensus GATA binding site. GATA-4 cooperatively activates the Grp78 promoter with YY1, and the DNA binding domain of YY1 is necessary and sufficient for this cooperation. In addition, GATA-4 activation of the Grp78 promoter is enhanced by the nuclear form of ATF6, and this synergy is further potentiated by YY1. These results suggest that during early heart organogenesis, Grp78 can be activated through cooperation between the cell type-specific transcription factors and ERSE-binding factors.

Received for publication, May 26, 2005 , and in revised form, January 18, 2006.

^* This work was supported in part by NCI, National Institutes of Health, Grant R01CA27607 (to A. S. L.). Part of this work was conducted in a facility constructed with support from National Center for Research Resources, National Institutes of Health, Research Facilities Improvement Program Grants C06 RR014514-01, C06 RR10600-01, and C06 CA62528-01. 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.

¹ Supported in part by a Wright Foundation Award.

² To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, 1441 Eastlake Ave., Los Angeles, CA 90089-9176. Tel.: 323-865-0507; Fax: 323-865-0094; E-mail: amylee{at}hsc.usc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. Hua, B. Zhu, F. Rosa, N. Deblon, J. Adelaide, B. Kahn-Perles, D. Birnbaum, and J. Imbert A Negative Feedback Regulatory Loop Associates the Tyrosine Kinase Receptor ERBB2 and the Transcription Factor GATA4 in Breast Cancer Cells Mol. Cancer Res., March 1, 2009; 7(3): 402 - 414. [Abstract] [Full Text] [PDF]

				R. S. Viger, S. M. Guittot, M. Anttonen, D. B. Wilson, and M. Heikinheimo Role of the GATA Family of Transcription Factors in Endocrine Development, Function, and Disease Mol. Endocrinol., April 1, 2008; 22(4): 781 - 798. [Abstract] [Full Text] [PDF]

				C. C. Glembotski Endoplasmic Reticulum Stress in the Heart Circ. Res., November 9, 2007; 101(10): 975 - 984. [Abstract] [Full Text] [PDF]

				A. S. Lee GRP78 Induction in Cancer: Therapeutic and Prognostic Implications Cancer Res., April 15, 2007; 67(8): 3496 - 3499. [Abstract] [Full Text] [PDF]

				S. Luo, C. Mao, B. Lee, and A. S. Lee GRP78/BiP Is Required for Cell Proliferation and Protecting the Inner Cell Mass from Apoptosis during Early Mouse Embryonic Development Mol. Cell. Biol., August 1, 2006; 26(15): 5688 - 5697. [Abstract] [Full Text] [PDF]