TY  - JOUR
AU  - Seidel, Philipp
AU  - Remus, Martina
AU  - Delacher, Michael
AU  - Grigaravicius, Paulius
AU  - Reuss, David E
AU  - Frappart, Lucien
AU  - von Deimling, Andreas
AU  - Feuerer, Markus
AU  - Abdollahi, Amir
AU  - Frappart, Pierre-Olivier
TI  - Epidermal Nbn deletion causes premature hair loss and a phenotype resembling psoriasiform dermatitis.
JO  - OncoTarget
VL  - 7
IS  - 17
SN  - 1949-2553
CY  - [S.l.]
PB  - Impact Journals LLC
M1  - DKFZ-2017-05616
SP  - 23006 - 23018
PY  - 2016
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:27050272
C2  - pmc:PMC5029606
DO  - DOI:10.18632/oncotarget.8470
UR  - https://inrepo02.dkfz.de/record/130537
ER  -