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@ARTICLE{Seidel:130537,
author = {P. Seidel and M. Remus and M. Delacher$^*$ and P.
Grigaravicius$^*$ and D. E. Reuss and L. Frappart and A. von
Deimling$^*$ and M. Feuerer$^*$ and A. Abdollahi$^*$ and
P.-O. Frappart$^*$},
title = {{E}pidermal {N}bn deletion causes premature hair loss and a
phenotype resembling psoriasiform dermatitis.},
journal = {OncoTarget},
volume = {7},
number = {17},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {DKFZ-2017-05616},
pages = {23006 - 23018},
year = {2016},
abstract = {Nijmegen Breakage Syndrome is a disease caused by NBN
mutations. Here, we report a novel function of Nbn in skin
homeostasis. We found that Nbn deficiency in hair follicle
(HF) progenitors promoted increased DNA damage signaling,
stimulating p16Ink4a up-regulation, Trp53 stabilization and
cytokines secretion leading to HF-growth arrest and hair
loss. At later stages, the basal keratinocytes layer
exhibited also enhanced DNA damage response but in contrast
to the one in HF progenitor was not associated with
pro-inflammatory cytokines expression, but rather increased
proliferation, lack of differentiation and immune response
resembling psoriasiform dermatitis. Simultaneous Nbn and
Trp53 inactivation significantly exacerbated this phenotype,
due to the lack of inhibition of pro-inflammatory cytokines
secretion by Trp53. Altogether, we demonstrated novel
functions of Nbn in HF maintenance and prevention of skin
inflammation and we provide a mechanistic explanation that
links cell intrinsic DNA maintenance with large scale
morphological tissue alterations.},
cin = {D100 / E210 / G380 / L101},
ddc = {610},
cid = {I:(DE-He78)D100-20160331 / I:(DE-He78)E210-20160331 /
I:(DE-He78)G380-20160331 / I:(DE-He78)L101-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27050272},
pmc = {pmc:PMC5029606},
doi = {10.18632/oncotarget.8470},
url = {https://inrepo02.dkfz.de/record/130537},
}