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

J. Biol. Chem., Vol. 282, Issue 9, 6316-6323, March 2, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/9/6316    most recent M607526200v1 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 Wlodarski, P. Articles by Wasik, M. A. Search for Related Content PubMed PubMed Citation Articles by Wlodarski, P. Articles by Wasik, M. A. Social Bookmarking                      What's this?

PU.1 Activates Transcription of SHP-1 Gene in Hematopoietic Cells^*

Pawel Wlodarski, Qian Zhang, Xiaobin Liu, Monika Kasprzycka^¶, Michal Marzec, and Mariusz A. Wasik¹

From the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and the Departments of Histology and Embryology, and ^¶Clinical Immunology, Warsaw Medical University, 02004 Warsaw, Poland

Protein-tyrosine phosphatase SHP-1 is the key negative regulator of numerous signaling pathways. SHP-1 is expressed in the hematopietic and epithelial cells as two structurally similar mRNA transcripts controlled by two different promoters designated P2 and P1, respectively. Whereas the transcriptional regulation of the SHP-1 gene P1 promoter has been partially elucidated, the structure and functional control of the P2 promoter remain unknown despite the critical role played by SHP-1 in the normal and malignant lymphoid and other hematopoetic cells. Using luciferase reporter assays with the set of constructs that contained a gradually truncated intron 1 of the SHP-1 gene, we identified the minimal (<120 bp) fragment that is able to fully activate expression of the reporter gene. Furthermore, we found that PU.1 (a member of the Ets transcription factor family that plays a crucial role in differentiation and function of the lymphoid and myeloid cells) binds to the identified P2 promoter both in vitro and in vivo. PU.1 also activates the promoter in the sequence specific manner and is critical for its expression as evidenced by the profound supression of the SHP-1 gene transcription upon the siRNA-mediated depletion of PU.1. These findings provide an insight into the structure of the hematopoietic cell-specific P2 promoter of the SHP-1 gene and identify PU.1 as the transcriptional activator of the P2 promoter.

Received for publication, August 7, 2006 , and in revised form, January 10, 2007.

^* This work was supported in part by the NCI/National Institutes of Health Grants R01-CA89194 and R01-CA96856. 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 To whom correspondence should be addressed: Dept. of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, 3400 Spruce St., 7.106 Founders Pavilion, Philadelphia, PA 19104-4283. Tel.: 215-662-3467; Fax: 215-662-7594; E-mail: wasik{at}mail.med.upenn.edu.

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

This article has been cited by other articles:

				K. Nakase, J. Cheng, Q. Zhu, and W. A. Marasco Mechanisms of SHP-1 P2 promoter regulation in hematopoietic cells and its silencing in HTLV-1-transformed T cells J. Leukoc. Biol., January 1, 2009; 85(1): 165 - 174. [Abstract] [Full Text] [PDF]

				J. Cheng, A. R. Kydd, K. Nakase, K. M. Noonan, A. Murakami, H. Tao, M. Dwyer, C. Xu, Q. Zhu, and W. A. Marasco Negative regulation of the SH2-homology containing protein-tyrosine phosphatase-1 (SHP-1) P2 promoter by the HTLV-1 Tax oncoprotein Blood, September 15, 2007; 110(6): 2110 - 2120. [Abstract] [Full Text] [PDF]