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

J. Biol. Chem., Vol. 282, Issue 34, 24915-24927, August 24, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/34/24915    most recent M701789200v1 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 Philips, A. S. Articles by Chong, B. H. Search for Related Content PubMed PubMed Citation Articles by Philips, A. S. Articles by Chong, B. H. Social Bookmarking                      What's this?

Analysis of the Signals and Mechanisms Mediating Nuclear Trafficking of GATA-4

LOSS OF DNA BINDING IS ASSOCIATED WITH LOCALIZATION IN INTRANUCLEAR SPECKLES^*

From the Centre for Vascular Research, Department of Medicine, St. George Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia

Nucleocytoplasmic transport of GATA-4 is important in maintaining and regulating normal cardiogenesis and heart function. This report investigates the detailed mechanisms of GATA-4 nuclear transport. We characterized a nonclassical nuclear localization signal between amino acids 270 and 324 that actively transports GATA-4 into the nucleus of both HeLa cells and cardiac myocytes. Fine mapping studies revealed four crucial arginine residues within this region that mediate active transport predominately through the nonclassical pathway via interaction with importin . These four residues were also essential for the DNA binding activity of GATA-4 and transcriptional activation of cardiac-specific genes. Interestingly, mutation of these residues not only inhibited DNA binding and gene transcription but also resulted in a preferential accumulation of the GATA-4 protein in distinct subnuclear speckles. A cardiac myocyte-specific, chromosome maintenance region 1-dependent nuclear export signal consisting of three essential leucine residues was also identified. The current study provides detailed information on the nuclear shuttling pathways of GATA-4 that represents an additional mechanism of gene regulation.

Received for publication, March 1, 2007 , and in revised form, May 31, 2007.

^* This work was supported by Program Grant 209618 from the National Health and Medical Research Council of Australia. 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.

¹ These authors contributed equally to this work.

² Supported by an Australian Postgraduate Award.

³ Supported by National Heart Foundation of Australia John Shaw Postdoctoral Research Fellowship PS04S1763. To whom correspondence should be addressed: Dept. of Medicine, WR Pitney Bldg., St. George Hospital, Gray St., Kogarah, NSW 2217, Australia. Tel.: 612-9350-2010; Fax: 612-9350-3998; E-mail: j.kwok{at}unsw.edu.au.

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

This article has been cited by other articles:

				S. Hussain, S. Perlman, and T. M. Gallagher Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Hepatitis Virus Infections by More than One Mechanism J. Virol., July 15, 2008; 82(14): 7212 - 7222. [Abstract] [Full Text] [PDF]