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

Laboratory of Immunology, Department of Biological Science, Institute for Basic Science, Sungkyunkwan University, Suwon 440-746, Korea.
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-alpha or H(2)O(2), 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.
Mesh Terms:
Apoptosis, Cell Line, Dexamethasone, Humans, Hydrogen Peroxide, Interferon-gamma, Jurkat Cells, Oxidative Stress, Protein Methyltransferases, Protein Tyrosine Phosphatases, RNA, Messenger, RNA, Small Interfering, Reactive Oxygen Species, Suppressor of Cytokine Signaling Proteins, T-Lymphocytes, Thioredoxins, Transfection, Tumor Necrosis Factor-alpha, Up-Regulation
Oncogene Sep. 03, 2009; 28(35);3145-56 [PUBMED:19561639]
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