Mitochondrial targeting of JNK/SAPK in the phorbol ester response of myeloid leukemia cells

The results show that TPA induces the association of stress-activated protein kinase with the mitochondrial anti-apoptotic Bcl-xL protein

Y Ito; N C Mishra; K Yoshida; S Kharbanda; S Saxena; D Kufe


Scholarcy highlights

  • Other studies have shown that TPA treatment of myeloid leukemia cells is associated with induction of the stressactivated protein kinase) and that this response is dependent on PKCb expression
  • The results demonstrate that TPA induces over a fivefold increase in mitochondrial levels of SAPK
  • Purity of the mitochondrial fraction was assessed by immunoblotting with antibodies against the cytoplasmic b-actin protein, the ERassociated calreticulin, the nuclear proliferating cell nuclear antigen protein and the cell membrane platelet-derived growth factor receptor
  • The selectivity of TPA-induced translocation of SAPK was supported by the absence of detectable changes in mitochondrial levels of extracellular signal regulated kinase 1/2
  • To determine whether targeting SAPK to mitochondria is associated with apoptosis, U-937, TUR and TUR/PKCb cells were studied for TPA-induced release of mitochondrial cytochrome c and activation of caspase-3
  • These findings support a model in which TPA-induced activation of the PKCb?stress-activated protein kinase pathway contributes to terminal monocytic differentiation by targeting SAPK to Bcl-xL in mitochondria and inducing cytochrome c release, caspase-3 activation and apoptosis

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