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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3311-3313. Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2002-12-3816. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3816v1 102/9/3311    most recent 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ungureanu, D. Articles by Silvennoinen, O. Search for Related Content PubMed PubMed Citation Articles by Ungureanu, D. Articles by Silvennoinen, O. Related Collections Signal Transduction Brief Reports Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Brief report PIAS proteins promote SUMO-1 conjugation to STAT1 Daniela Ungureanu, Sari Vanhatupa, Noora Kotaja, Jie Yang, Saara Aittomäki, Olli A. Jänne, Jorma J. Palvimo, and Olli Silvennoinen From the Institute of Medical Technology, University of Tampere, Finland; Department of Clinical Microbiology, Tampere University Hospital, Finland; Biomedicum Helsinki, Institute of Biomedicine, Helsinki, Finland; and Department of Clinical Chemistry, University of Helsinki, Finland. Signal transducer and activator of transcription 1 (STAT1) is a critical mediator of interferon- (IFN-)–induced transcription that is regulated through posttranslational modifications and through transacting proteins such as protein inhibitor of activated STAT1 (PIAS1). PIAS proteins have been shown to function as E3-type small ubiquitin-like modifier (SUMO) ligases, and sumoylation has been identified as a modulatory mechanism for several transcription factors. Here we show that STAT1 is subject to SUMO-1 modification, and sumoylation occurs in vivo and in vitro at a single, evolutionary conserved amino acid residue Lys703. Members of the PIAS family of proteins were found to strongly stimulate sumoylation of STAT1. Furthermore, activation of STAT1 by IFN- or pervanadate induced SUMO-1 conjugation. Mutation of Lys703 in STAT1 resulted in increased IFN-–mediated transactivation, suggesting a negative regulatory function for sumoylation. These results indicate that STAT1 is covalently modified by SUMO-1 in cytokine signaling and that PIAS proteins promote SUMO-1 conjugation to STAT1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Catala, J. Ouyang, I. A. Abreu, Y. Hu, H. Seo, X. Zhang, and N.-H. Chua The Arabidopsis E3 SUMO Ligase SIZ1 Regulates Plant Growth and Drought Responses PLANT CELL, September 1, 2007; 19(9): 2952 - 2966. [Abstract] [Full Text] [PDF] Md. M. Ali, T. Yoshizawa, O. Ishibashi, A. Matsuda, M. Ikegame, J. Shimomura, H. Mera, K. Nakashima, and H. Kawashima PIASxbeta is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts J. Cell Sci., August 1, 2007; 120(15): 2565 - 2573. [Abstract] [Full Text] [PDF] L. Song, S. Bhattacharya, A. A. Yunus, C. D. Lima, and C. Schindler Stat1 and SUMO modification Blood, November 15, 2006; 108(10): 3237 - 3244. [Abstract] [Full Text] [PDF] N. I. Arbouzova and M. P. Zeidler JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions. Development, July 1, 2006; 133(14): 2605 - 2616. [Abstract] [Full Text] [PDF] Z. Tang, O. E. Far, H. Betz, and A. Scheschonka Pias1 Interaction and Sumoylation of Metabotropic Glutamate Receptor 8 J. Biol. Chem., November 18, 2005; 280(46): 38153 - 38159. [Abstract] [Full Text] [PDF] E. van den Akker, S. Ano, H.-M. Shih, L.-C. Wang, M. Pironin, J. J. Palvimo, N. Kotaja, O. Kirsh, A. Dejean, and J. Ghysdael FLI-1 Functionally Interacts with PIASx{alpha}, a Member of the PIAS E3 SUMO Ligase Family J. Biol. Chem., November 11, 2005; 280(45): 38035 - 38046. [Abstract] [Full Text] [PDF] G. Forget, D. J. Gregory, and M. Olivier Proteasome-mediated Degradation of STAT1{alpha} following Infection of Macrophages with Leishmania donovani J. Biol. Chem., August 26, 2005; 280(34): 30542 - 30549. [Abstract] [Full Text] [PDF] K. Nakagawa and N. Kuzumaki Transcriptional activity of megakaryoblastic leukemia 1 (MKL1) is repressed by SUMO modification Genes Cells, August 1, 2005; 10(8): 835 - 850. [Abstract] [Full Text] [PDF] D. Ungureanu, S. Vanhatupa, J. Gronholm, J. J. Palvimo, and O. Silvennoinen SUMO-1 conjugation selectively modulates STAT1-mediated gene responses Blood, July 1, 2005; 106(1): 224 - 226. [Abstract] [Full Text] [PDF] E. Munarriz, D. Barcaroli, A. Stephanou, P. A. Townsend, C. Maisse, A. Terrinoni, M. H. Neale, S. J. Martin, D. S. Latchman, R. A. Knight, et al. PIAS-1 Is a Checkpoint Regulator Which Affects Exit from G1 and G2 by Sumoylation of p73 Mol. Cell. Biol., December 15, 2004; 24(24): 10593 - 10610. [Abstract] [Full Text] [PDF] W. Roth, C. Sustmann, M. Kieslinger, A. Gilmozzi, D. Irmer, E. Kremmer, C. Turck, and R. Grosschedl PIASy-Deficient Mice Display Modest Defects in IFN and Wnt Signaling J. Immunol., November 15, 2004; 173(10): 6189 - 6199. [Abstract] [Full Text] [PDF] S. Truchet, M. Chebrout, C. Djediat, J. Wietzerbin, and P. 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