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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3237-3244. Prepublished online as a Blood First Edition Paper on July 20, 2006; DOI 10.1182/blood-2006-04-020271. This Article Full Text (PDF) Supplemental Table All Versions of this Article: blood-2006-04-020271v1 108/10/3237    most recent Alert me when this article is cited Alert me if a correction is posted 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 Song, L. Articles by Schindler, C. Search for Related Content PubMed PubMed Citation Articles by Song, L. Articles by Schindler, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 6, 2006 Accepted June 27, 2006 Stat1 and SUMO modification Li Song, Samita Bhattacharya, Ali A Yunus, Christopher D Lima, and Christian Schindler* Microbiology, Columbia University Structural Biology Program, Memorial Sloan-Kettering Cancer Center Medicine, Columbia University * Corresponding author; email: cws4{at}columbia.edu. Many proteins are known to undergo SUMO (Small Ubiquitin- related Modifiers) modification by an E1, E2 and E3 dependent ligation process. Recognition that PIAS (Protein Inhibitor of Activated STATs) proteins are SUMO E3 ligases raised the possibility that STATs may also be regulated by SUMO modification. Consistent with this possibility, a SUMOylation consensus site (KxE; = hydrophobic residue, x = any residue) was identified in Stat1 (i.e., 702IKTE705), but not in other STATs. Biochemical analysis confirmed that Stat1 K703 could be SUMO modified in vitro. Mutation of this critical lysine (i.e., Stat1K703R) yielded a protein, which when expressed in Stat1-/- MEFs, exhibited enhanced DNA binding and nuclear retention. This was associated with modest changes in transcriptional and antiviral activity. However, mutation of second critical residue in the SUMO consensus site, E705 (i.e., Stat1E705A), yielded a protein with wild type DNA binding, nuclear retention, transcriptional and antiviral activity. Similar observations were made when these mutants were expressed in primary Stat1-/- macrophages. These observations suggest that although Stat1 can uniquely be SUMOylated in vitro, this modification is unlikely to play an important role in regulating Stat1 activity in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. Zhao, C. Lee, R. Piganis, C. Plumlee, N. de Weerd, P. J. Hertzog, and C. Schindler A Conserved IFN-{alpha} Receptor Tyrosine Motif Directs the Biological Response to Type I IFNs J. Immunol., April 15, 2008; 180(8): 5483 - 5489. [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] C. Schindler, D. E. Levy, and T. Decker JAK-STAT Signaling: From Interferons to Cytokines J. Biol. Chem., July 13, 2007; 282(28): 20059 - 20063. [Full Text] [PDF] W. Zhao, E. N. Cha, C. Lee, C. Y. Park, and C. Schindler Stat2-Dependent Regulation of MHC Class II Expression J. Immunol., July 1, 2007; 179(1): 463 - 471. [Abstract] [Full Text] [PDF]

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