Thirty-eight-negative kinase 1 (TNK1) facilitates TNFalpha-induced apoptosis by blocking NF-kappaB activation

Oncogene. 2007 Oct 4;26(45):6536-45. doi: 10.1038/sj.onc.1210476. Epub 2007 Apr 30.


Thirty-eight-negative kinase 1 (TNK1) is a member of the ACK-family of nonreceptor tyrosine kinases and was originally cloned from CD34+/Lin-/CD38-hematopoietic stem/progenitor cells. The signaling pathways induced by TNK1 are largely unknown. Here, we report that expression and consequent activation of TNK1 enables tumor necrosis factor alpha (TNFalpha)-induced apoptosis by selectively inhibiting TNFalpha-induced activation of nuclear factor-kappaB (NF-kappaB). TNK1 has no effect on NF-kappaB DNA binding or the composition of the NF-kappaB complex; however, the kinase markedly prevents TNFalpha-induced NF-kappaB transactivation. TNK1 therefore acts as a novel molecular switch that can determine the properties of TNFalpha signaling and therefore cell death.

MeSH terms

  • Apoptosis
  • Caspases / metabolism
  • Fetal Proteins / physiology*
  • HeLa Cells
  • Humans
  • NF-kappa B / metabolism*
  • Protein-Tyrosine Kinases / physiology*
  • Signal Transduction
  • Transcription Factor RelA / physiology
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / physiology*


  • Fetal Proteins
  • NF-kappa B
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Protein-Tyrosine Kinases
  • TNK1 protein, human
  • Caspases