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J. Biol. Chem., Vol. 279, Issue 17, 16996-17003, April 23, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/17/16996    most recent M311752200v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hong, S. Articles by Cheong, J. Search for Related Content PubMed PubMed Citation Articles by Hong, S. Articles by Cheong, J. Social Bookmarking                      What's this?

Activation and Interaction of ATF2 with the Coactivator ASC-2 Are Responsive for Granulocytic Differentiation by Retinoic Acid^*

SunHwa Hong, Hyun Mi Choi, Min Jung Park, Young Hee Kim, Yoon Ha Choi, Hyung Hoi Kim, Young Hyun Choi¶, and JaeHun Cheong||

From the Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, the Department of Clinical Pathology, College of Medicine, Pusan National University, Busan 602-739, and the ^¶Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan 614-054, Korea

Terminal differentiation of hematopoietic cells follows a precisely orchestrated program of transcriptional regulatory events at the promoters of both lineage-specific and ubiquitous genes. Here we show that the transcription factor ATF2 is associated with the induction of granulocytic differentiation, and the molecular interaction of ATF2 with a tissue-specific coactivator activating signal cointegator-2 (ASC-2) potentiates the differentiation procedure. All-trans retinoic acid (RA) induced the phosphorylation and expression of ATF2 in the early and middle phase of granulocyte differentiation, respectively. The activation of granulocyte-specific gene expression is increased with the concerted action of another basic regionleucine zipper factor, CCAAT/enhancer-binding protein (C/EBP), and ASC-2, which function in a cooperative manner. The interaction between ATF2 and C/EBP in RA-treated cells was enhanced by the ectopic expression of ASC-2. ATF2-mediated transactivation was also increased by co-transfection of ASC-2. This resulted from the direct protein interaction that the N-terminal transactivation domain of ATF2 interacts with the central region of ASC-2. Furthermore, the molecular interaction of ATF2 and ASC-2 was stimulated by RA treatment and inhibited by p38 kinase inhibitor. Taking these results together, these results suggest that the differentiation-dependent expression and phosphorylation of ATF2 protein physically and functionally interacts with C/EBP and coativator ASC-2 and synergizes to induce target gene transcription during granulocytic differentiation.

Received for publication, October 27, 2003 , and in revised form, January 5, 2004.

^* This research was supported by a grant of the Korea Health Ministry of Health and Welfare, Republic of Korea (Grant. 02-PJ1-PG3-20908-0009) 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.

^|| To whom correspondence should be addressed. Tel.: 82-51-510-2277; Fax: 82-51-513-9258; E-mail: molecule85{at}pusan.ac.kr.

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