TY  - JOUR
AU  - Zupancic, Tina
AU  - Sersa, Gregor
AU  - Törmä, Hans
AU  - Lane, Ellen Birgitte
AU  - Herrmann, Harald
AU  - Komel, Radovan
AU  - Liovic, Mirjana
TI  - Keratin gene mutations influence the keratinocyte response to DNA damage and cytokine induced apoptosis.
JO  - Archives of dermatological research
VL  - 309
IS  - 7
SN  - 1432-069X
CY  - Berlin
PB  - Springer
M1  - DKFZ-2017-04259
SP  - 587 - 593
PY  - 2017
AB  - 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-α 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-α 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:28647894
DO  - DOI:10.1007/s00403-017-1757-9
UR  - https://inrepo02.dkfz.de/record/128242
ER  -