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  • Keratin gene mutations influence the keratinocyte response to DNA damage and cytokine induced apoptosis
    Zupančič, Tina, 1982- ...
    The keratin filament cytoskeleton is vital to the normal function of epithelial cells. It provides structural support and regulates different aspects of cell metabolism. Mutations in keratins 5 and ... 14 cause a skin fragility disorder, epidermolysis bullosa simplex (EBS). Patients with severe EBS have an increased cumulative risk for basal cell carcinoma. In this study, we tested how keratin 5 and 14 mutant EBS patient-derived keratinocytes behave in the face of two different types of stressors that are able to induce cell death: ionizing radiation and cytokines TNF-a and TRAIL. The data point out to a substantial difference between how normal and keratin mutant keratinocytes deal with such stresses. When case of DNA damage, the ATM/ Chk2-pathway is one of the two main tracks that can prevent the progression of mitosis and so allow repair. This was altered in all investigated keratin mutants with a particular down-regulation of the activated form of checkpoint kinase 2 (pChk2). Keratin mutants also appear less sensitive than normal cells to treatment with TNF-a or TRAIL, and this may be linked to the up-regulation of two pro-survival proteins, Bcl-2 and FLIP. Such changes are likely to have a profound effect on mutant keratinocytes ability to survive and withstand stress, and in theory this may be also a contributing factor to cell transformation.
    Vir: Archives for dermatological research. - ISSN 0340-3696 (Vol. 309, iss. 7, Sep. 2017, str. 587-593)
    Vrsta gradiva - članek, sestavni del ; neleposlovje za odrasle
    Leto - 2017
    Jezik - angleški
    COBISS.SI-ID - 33302745
    DOI

vir: Archives for dermatological research. - ISSN 0340-3696 (Vol. 309, iss. 7, Sep. 2017, str. 587-593)
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