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Blood, 1 July 2005, Vol. 106, No. 1, pp. 224-226.
Prepublished online as a Blood First Edition Paper on March 10, 2005; DOI 10.1182/blood-2004-11-4514.
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Submitted November 30, 2004
Accepted February 24, 2005
SUMO-1 conjugation selectively modulates STAT1-mediated gene responses
Daniela Ungureanu, Sari Vanhatupa, Juha Gronholm, Jorma J Palvimo, and Olli Silvennoinen*
Institute of Medical Technology, University of Tampere, Tampere, Finland
Department of Clinical Microbiology, Tampere University Hospital, Tampere, Finland
Institute of Medical Technology, University of Tampere, Tampere, Finland; Department of Medical Biochemistry, University of Kuopio, Kuopio, Finland
* Corresponding author; email: olli.silvennoinen{at}uta.fi.
STAT1 is a critical mediator of interferon (IFN)-induced gene responses. Recently, STAT1 was found to become modified by SUMO-1 conjugation at Lys703 through the SUMO E3 ligase function of PIAS proteins. However, the physiological function of sumoylation in STAT1 is still unclear. Here, we show that mutations in SUMO attachment site in STAT1 result in increased transcriptional activity in a fashion that is selective among IFN-gamma target genes. Sumoylation defective STAT1 mutant displayed increased induction of GBP1 and TAP1 transcription but not IRF-1 transcription. Moreover, the sumoylation defective mutant STAT1-KR showed a prolonged DNA-binding activity and nuclear localisation in response to IFN-gamma stimulation. These results suggest that sumoylation has a defined negative regulatory effect on selective STAT1-mediated transcription responses.

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