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

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services 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 Rouyez, M.-C. Articles by Dusanter-Fourt, I. Search for Related Content PubMed PubMed Citation Articles by Rouyez, M.-C. Articles by Dusanter-Fourt, I.

IFN Regulatory Factor-2 Cooperates with STAT1 to Regulate Transporter Associated with Antigen Processing-1 Promoter Activity¹

Marie-Christine Rouyez^*, Marta Lestingi^*, Martine Charon^*, Serge Fichelson^*, Agnès Buzyn and Isabelle Dusanter-Fourt^2,*

Departments of ^* Hematology and Immunology, Institut Cochin, Paris, France

Class I MHC complexes (MHC_I) are essential in mediating immune response. The transport of antigenic peptides (TAP) to MHC_I and the stable expression of MHC_I on the cell surface require the presence of a dedicated TAP. In this study we report that IFN- and thrombopoietin (TPO) strongly increase TAP1 protein expression in megakaryocytes, followed by an enhanced expression of MHC_I on the cell surface. This expression parallels the enhanced TAP1 promoter activity and TAP1 mRNA expression, which are independent of protein synthesis. We also show that this cytokine-dependent expression of TAP1 transcripts depends on STAT1 and IFN regulatory factor-2 (IRF-2), but not on IRF-1, and provide evidence that IRF-2 constitutively binds to the TAP1 gene promoter and enhances TAP1 promoter activity. We show that IRF-2 forms a complex with STAT1 and the cytokine-responsive region of the TAP1 promoter in any TPO or IFN- target cells tested. Interaction of IRF-2 and STAT1 on the promoter depends on the DNA-binding domain of IRF-2. Overall, our data indicate that TPO and IFN- activate the expression of TAP1 via a new mechanism that involves functional cooperation between STAT1 and IRF-2 on the TAP1 promoter.

This article has been cited by other articles:

				Y. Wang, D. Liu, P. Chen, H. P. Koeffler, X. Tong, and D. Xie Negative Feedback Regulation of IFN-{gamma} Pathway by IFN Regulatory Factor 2 in Esophageal Cancers Cancer Res., February 15, 2008; 68(4): 1136 - 1143. [Abstract] [Full Text] [PDF]

				K. Schroder, M. Spille, A. Pilz, J. Lattin, K. A. Bode, K. M. Irvine, A. D. Burrows, T. Ravasi, H. Weighardt, K. J. Stacey, et al. Differential Effects of CpG DNA on IFN-beta Induction and STAT1 Activation in Murine Macrophages versus Dendritic Cells: Alternatively Activated STAT1 Negatively Regulates TLR Signaling in Macrophages J. Immunol., September 15, 2007; 179(6): 3495 - 3503. [Abstract] [Full Text] [PDF]

				W. Wang, H. D. Edington, U. N.M. Rao, D. M. Jukic, S. R. Land, S. Ferrone, and J. M. Kirkwood Modulation of Signal Transducers and Activators of Transcription 1 and 3 Signaling in Melanoma by High-Dose IFN{alpha}2b Clin. Cancer Res., March 1, 2007; 13(5): 1523 - 1531. [Abstract] [Full Text] [PDF]

				R. M. Tooze, S. Stephenson, and G. M. Doody Repression of IFN-{gamma} Induction of Class II Transactivator: A Role for PRDM1/Blimp-1 in Regulation of Cytokine Signaling J. Immunol., October 1, 2006; 177(7): 4584 - 4593. [Abstract] [Full Text] [PDF]