title: The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities.
abstract: The suppressor of cytokine signaling (SOCS) proteins are a family of cytokine-inducible negative regulators of cytokine signaling. Interferon (IFN)-gamma treatment induces the expression of SOCS1, SOCS2, and SOCS3 mRNAs. To examine the effect of SOCS proteins on IFN-mediated Janus-activated kinase/signal transducers and activators of transcription (STAT) signaling, HeLa- and MCF-7-derived stable cell lines expressing SOCS1, SOCS2, and SOCS3 proteins were established. SOCS1 and SOCS3 but not SOCS2 inhibited the tyrosine phosphorylation and nuclear translocation of STAT1 in response to IFN stimulation. The IFN-mediated antiviral and antiproliferative activities were consistently blocked by the constitutive expression of SOCS1 and SOCS3 but not SOCS2 proteins. The maximum inhibitory activities of SOCS1 and SOCS3 proteins toward the activation of STAT1 were observed at very low levels of SOCS protein expression. In addition, SOCS1 exhibited a much stronger inhibitory activity toward the activation of STAT1 than did SOCS3. These results suggest that SOCS1 and SOCS3 but not SOCS2 are inhibitors of IFN-mediated Janus-activated kinase/STAT signaling pathways.
authors.affiliation: Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Song
authors.forename: K
authors.initials: K
authors.lastname: Shuai
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C106643:SOCS2 protein, human; C106644:SOCS3 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases