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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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IMMUNOBIOLOGY
Brief report

SUMO-1 conjugation selectively modulates STAT1-mediated gene responses

Daniela Ungureanu, Sari Vanhatupa, Juha Grönholm, Jorma J. Palvimo, and Olli Silvennoinen

From the Institute of Medical Technology, University of Tampere, Tampere, Finland; Department of Clinical Microbiology, Tampere University Hospital, Tampere, Finland; and Department of Medical Biochemistry, University of Kuopio, Kuopio, Finland.

Signal transducers and activators of transcription 1 (STAT1) is a critical mediator of interferon (IFN)–induced gene responses. Recently, STAT1 was found to become modified by small ubiquitin-like modifier 1 (SUMO-1) conjugation at Lys703 through the SUMO E3 ligase function of protein inhibitors of activated STAT (PIAS) proteins. However, the physiologic function of sumoylation in STAT1 is still unclear. Here, we show that mutations in the SUMO attachment site in STAT1 result in increased transcriptional activity in a fashion that is selective among IFN-{gamma} target genes. The sumoylation-defective STAT1 mutant displayed increased induction of guanylate-binding protein 1 (GBP1) and transporters associated with antigen presentation 1 (TAP1) transcription but not interferon regulatory factor 1 (IRF1) transcription. Moreover, the sumoylation-defective mutant STAT1-KR showed a prolonged DNA-binding activity and nuclear localization 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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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.
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