Abstract
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 α (TNFα)-induced apoptosis by selectively inhibiting TNFα-induced activation of nuclear factor-κB (NF-κB). TNK1 has no effect on NF-κB DNA binding or the composition of the NF-κB complex; however, the kinase markedly prevents TNFα-induced NF-κB transactivation. TNK1 therefore acts as a novel molecular switch that can determine the properties of TNFα signaling and therefore cell death.
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Work in the lab of TS and SF is supported by the DFG (Clinical Research Group 167).
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Azoitei, N., Brey, A., Busch, T. et al. Thirty-eight-negative kinase 1 (TNK1) facilitates TNFα-induced apoptosis by blocking NF-κB activation. Oncogene 26, 6536–6545 (2007). https://doi.org/10.1038/sj.onc.1210476
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DOI: https://doi.org/10.1038/sj.onc.1210476
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