UVC-induced apoptosis in Dubca cells is independent of JNK activation and p53Ser-15 phosphorylation

Shahanas Chathoth, Faisal Thayyullathil, Abdulkader Hago, Allen Shahin, Mahendra Patel, Sehamuddin Galadari

Research output: Contribution to journalArticlepeer-review

Abstract

Ultraviolet C (UVC) irradiation in mammalian cell lines activates a complex signaling network that leads to apoptosis. By using Dubca cells as a model system, we report the presence of a UVC-induced apoptotic pathway that is independent of c-Jun N-terminal kinases (JNKs) activation and p53 phosphorylation at Ser15. Irradiation of Dubca cells with UVC results in a rapid JNK activation and phosphorylation of its downstream target c-Jun, as well as, phosphorylation of activating transcription factor 2 (ATF2). Pre-treatment with JNK inhibitor, SP600125, inhibited UVC-induced c-Jun phosphorylation without preventing UVC-induced apoptosis. Similarly, inhibition of UVC-induced p53 phosphorylation did not prevent Dubca cell apoptosis, suggesting that p53Ser-15 phosphorylation is not associated with UVC-induced apoptosis signaling. The pan-caspase inhibitor z-VAD-fmk inhibited UVC-induced PARP cleavage, DNA fragmentation, and ultimately apoptosis of Dubca cells. Altogether, our study clearly indicates that UVC-induced apoptosis is independent of JNK and p53 activation in Dubca cells, rather, it is mediated through a caspase dependent pathway. Our findings are not in line with the ascribed critical role for JNKs activation, and downstream phosphorylation of targets such as c-Jun and ATF2 in UVC-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)426-432
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume383
Issue number4
DOIs
StatePublished - Jun 12 2009

Keywords

  • ATF2
  • Apoptosis
  • Caspases
  • c-Jun
  • c-Jun N-terminal kinases
  • p53 phosphorylation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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