Avtor/Urednik		Zupančič, Tina; Serša, Gregor; Törmä, Hans; Ellen Birgitte, Lane; Herrmann, Harald; Komel, Radovan; Liović, Mirjana
Naslov		Keratin gene mutations influence the keratinocyte response to DNA damage and cytokine induced apoptosis
Tip		članek
Leto izdaje		2017
Obseg		str. str.
ISSN		0340-3696 - Archives for dermatological research. Archiv für dermatologische Forschung
Jezik		eng
Abstrakt		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.
Proste vsebinske oznake		keratin mutation DNA damage keratin mutacija poškodba DNA