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 journalArticle

    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

    Fingerprint

    Phosphorylation
    Phosphotransferases
    Chemical activation
    Apoptosis
    Activating Transcription Factor 2
    Cells
    Irradiation
    Caspase Inhibitors
    JNK Mitogen-Activated Protein Kinases
    DNA Fragmentation
    Caspases
    Cell Line
    DNA

    Keywords

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

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Cite this

    UVC-induced apoptosis in Dubca cells is independent of JNK activation and p53Ser-15 phosphorylation. / Chathoth, Shahanas; Thayyullathil, Faisal; Hago, Abdulkader; Shahin, Allen; Patel, Mahendra; Galadari, Sehamuddin.

    In: Biochemical and Biophysical Research Communications, Vol. 383, No. 4, 12.06.2009, p. 426-432.

    Research output: Contribution to journalArticle

    Chathoth, Shahanas ; Thayyullathil, Faisal ; Hago, Abdulkader ; Shahin, Allen ; Patel, Mahendra ; Galadari, Sehamuddin. / UVC-induced apoptosis in Dubca cells is independent of JNK activation and p53Ser-15 phosphorylation. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 383, No. 4. pp. 426-432.
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