Activation of ERK during DNA damage-induced apoptosis involves protein kinase Cδ

Alakananda Basu, Haidi Tu

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


We have previously shown that protein kinase C (PKC) acts upstream of caspases to regulate cisplatin-induced apoptosis. Since extracellular signal-regulated kinases (ERKs) have also been implicated in DNA damage-induced apoptosis, we have examined if ERK signaling pathway acts downstream of PKC in the regulation of cisplatin-induced apoptosis. PKC activator PDBu induced ERK1/2 phosphorylation which was inhibited by general PKC inhibitor bisindolylmaleimide and Gö 6983 as well as the MEK inhibitor U0126 but not by the PKCδ inhibitor rottlerin. Cisplatin caused a concentration- dependent activation of ERK1/2 in HeLa cells. The level of ERK2 was decreased in HeLa cells that acquired resistance to cisplatin (HeLa/CP). The MEK inhibitor U0126 inhibited cisplatin-induced ERK activation and attenuated cisplatin-induced cell death. Inhibition of PKCδ by rottlerin or depletion of PKCδ by siRNA inhibited cisplatin-induced ERK activation. These results suggest that cisplatin-induced DNA damage results in activation of ERK1/2 via PKCδ.

Original languageEnglish
Pages (from-to)1068-1073
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - 9 Sep 2005


  • Apoptosis
  • Cisplatin
  • DNA damage
  • Drug-resistance
  • ERK
  • HeLa cells
  • PKCδ
  • Rottlerin
  • U0126
  • siRNA


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