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@ARTICLE{Zupancic:128242,
author = {T. Zupancic and G. Sersa and H. Törmä and E. B. Lane and
H. Herrmann$^*$ and R. Komel and M. Liovic},
title = {{K}eratin gene mutations influence the keratinocyte
response to {DNA} damage and cytokine induced apoptosis.},
journal = {Archives of dermatological research},
volume = {309},
number = {7},
issn = {1432-069X},
address = {Berlin},
publisher = {Springer},
reportid = {DKFZ-2017-04259},
pages = {587 - 593},
year = {2017},
abstract = {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.},
cin = {B065},
ddc = {610},
cid = {I:(DE-He78)B065-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28647894},
doi = {10.1007/s00403-017-1757-9},
url = {https://inrepo02.dkfz.de/record/128242},
}