The tumor suppressor activity of SOCS-1

Oncogene. 2002 Jun 27;21(28):4351-62. doi: 10.1038/sj.onc.1205537.


SOCS-1 is an inducible SH2-containing inhibitor of Jak kinases and as such can potently suppress cytokine signaling. SOCS-1 deficient mice die within the first three weeks of life from a myeloproliferative disorder driven by excessive interferon signaling. We report here that SOCS-1 inhibits proliferation signals induced by a variety of oncogenes active within the hematopoietic system. Ectopic expression of SOCS-1 abolished proliferation mediated by a constitutively active form of the KIT receptor, TEL-JAK2, and v-ABL, and reduced metastasis from BCR-ABL transformed cells. SOCS-1, however, did not interfere with v-SRC or RASV12 mediated cellular transformation. A mutant form of SOCS-1 unable to bind through its SH2 domain to tyrosine phosphorylated proteins could still inhibit KIT, but not TEL-JAK2, indicating multiple mechanisms for SOCS-1-mediated tumor suppression. We show that the steady state levels of TEL-JAK2 and to a greater extent v-ABL are diminished in the presence of SOCS-1. Lastly, we show that SOCS-1 -/- fibroblasts are more sensitive than wild type fibroblasts to either spontaneous or oncogene-induced transformation. These data suggest that loss-of-function of SOCS-1 may collaborate with a variety of hematopoietic oncogenes to facilitate tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins / physiology*
  • Cell Division
  • Cell Transformation, Neoplastic / metabolism
  • DNA-Binding Proteins / metabolism
  • Fibroblasts / metabolism
  • Fusion Proteins, bcr-abl / metabolism
  • Genes, Tumor Suppressor / physiology*
  • Hematopoietic Stem Cells / physiology*
  • Janus Kinase 2
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitogen-Activated Protein Kinases / metabolism
  • Oncogene Proteins v-abl / genetics
  • Oncogene Proteins v-abl / metabolism
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases / physiology
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism
  • Proto-Oncogene Proteins*
  • Repressor Proteins / physiology
  • Retroviridae / genetics
  • STAT1 Transcription Factor
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators / metabolism
  • Transfection
  • p38 Mitogen-Activated Protein Kinases
  • src Homology Domains


  • Carrier Proteins
  • DNA-Binding Proteins
  • Oncogene Proteins v-abl
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • STAT1 Transcription Factor
  • Socs1 protein, mouse
  • Stat1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • TEL-JAK2 fusion protein, human
  • TEL-JAK2 fusion protein, mouse
  • Trans-Activators
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-kit
  • Fusion Proteins, bcr-abl
  • JAK2 protein, human
  • Jak2 protein, mouse
  • Janus Kinase 2
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases