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SOCS1 protects protein tyrosine phosphatases by thioredoxin upregulation and attenuates Jaks to suppress ROS-mediated apoptosis

Oncogene volume 28, pages 3145–3156 (2009)Cite this article

Abstract

Suppressors of cytokine signaling (SOCS) are negative regulators of cytokine-induced signal transduction, which play multiple roles in cell growth, differentiation and apoptosis. In this study, the regulatory role of SOCS in oxidative stress-induced apoptosis was investigated. In Jurkat T cells and mouse splenocytes, we have found that SOCS1 is induced in response to tumor necrosis factor-α or H2O2, concomitant with the activation of Jaks which act as important mediators of reactive oxygen species (ROS)-induced apoptosis upstream of p38 mitogen-activated protein kinase. Using SOCS1 overexpressing or knockdown Jurkat T-cell systems we clearly demonstrate that, SOCS1 inhibits the ROS-mediated apoptosis. The antiapoptotic action of SOCS1 was exerted not only by suppressing Jaks, but also by sustaining protein tyrosine phosphatase (PTP) activities. Notably, SOCS1-transduced cells displayed increase in thioredoxin levels and decrease in ROS generation induced by oxidative stress. In addition, the Jak-inhibiting and PTP-sustaining effect of SOCS1 was significantly reduced on thioredoxin ablation. Moreover, coimmunoprecipitation data revealed molecular interaction of SHP1 or CD45 with thioredoxin, which was promoted in SOCS1-transfected cells. Together, our data strongly suggest that both the protection of PTPs by thioredoxin from ROS attack and the attenuation of Jaks account for the antiapoptotic function of SOCS1 in immune cells under oxidative stress.

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Abbreviations

H2DCFDA:

2′,7′-dichlorodihydrofluorescein diacetate; Jak,Janus tyrosine kinase

PTP:

protein tyrosine phosphatase

ROS:

reactive oxygen species

shRNA:

small hairpin RNA

siRNA:

small interference RNA

SOCS:

suppressors of cytokine signaling

Stat:

signal transducers and activators of transcription

Trx:

thioredoxin

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Acknowledgements

This work was supported by Brain Korea 21 program and research grants from KOSEF (2008-01752), KRF (314-2008-1:E00030) and MOHW (A084298). J Oh was supported in part by the 2005 Seoul Graduate Student Scholarship.

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Authors and Affiliations

  1. Department of Biological Science, Laboratory of Immunology, Institute for Basic Science, Sungkyunkwan University, Suwon, Korea

    J Oh & C-E Lee

  2. Department of Biochemistry and Molecular Biology, Brain Korea 21 Project for Medical Science, Yonsei University School of Medicine, Seoul, Korea

    M-W Hur

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  1. J Oh
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Correspondence to C-E Lee.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Oh, J., Hur, MW. & Lee, CE. SOCS1 protects protein tyrosine phosphatases by thioredoxin upregulation and attenuates Jaks to suppress ROS-mediated apoptosis. Oncogene 28, 3145–3156 (2009). https://doi.org/10.1038/onc.2009.169

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