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Sci. Signal., 21 July 2009
Vol. 2, Issue 80, p. ra37
[DOI: 10.1126/scisignal.1162191]

RESEARCH ARTICLES

Intracellular Delivery of a Cell-Penetrating SOCS1 that Targets IFN-{gamma} Signaling

Antonio DiGiandomenico, Lukasz S. Wylezinski, and Jacek Hawiger*

Department of Microbiology and Immunology, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN 37232–2363, USA.

Abstract: Suppressor of cytokine signaling–1 (SOCS1) is an intracellular inhibitor of the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway that couples interferon-{gamma} (IFN-{gamma}) signaling to the nucleus. Because several inflammatory diseases are associated with uncontrolled IFN-{gamma} signaling, we engineered a recombinant cell-penetrating SOCS1 (CP-SOCS1) to target this pathway. Here, we show that CP-SOCS1, analogous to endogenous SOCS1, interacted with components of the IFN-{gamma} signaling complex and functionally attenuated the phosphorylation of STAT1, which resulted in the subsequent inhibition of the production of proinflammatory chemokines and cytokines. Thus, controlled, intracellular delivery of recombinant CP-SOCS1 boosted the anti-inflammatory potential of the cell by restoring the homeostatic balance between pro- and anti-inflammatory signaling. This approach to controlling signal transduction has potential use for therapeutic targeting of signaling pathways associated with inflammatory diseases.

* To whom correspondence should be addressed. E-mail: jacek.hawiger{at}vanderbilt.edu

Citation: A. DiGiandomenico, L. S. Wylezinski, J. Hawiger, Intracellular Delivery of a Cell-Penetrating SOCS1 that Targets IFN-{gamma} Signaling. Sci. Signal. 2, ra37 (2009).

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