TY  - JOUR
A1  - Prieto García, Cristian
A1  - Hartmann, Oliver
A1  - Reissland, Michaela
A1  - Braun, Fabian
A1  - Fischer, Thomas
A1  - Walz, Susanne
A1  - Schülein‐Völk, Christina
A1  - Eilers, Ursula
A1  - Ade, Carsten P.
A1  - Calzado, Marco A.
A1  - Orian, Amir
A1  - Maric, Hans-Michael
A1  - Münch, Christian
A1  - Rosenfeldt, Mathias
A1  - Eilers, Martin
A1  - Diefenbacher, Markus Elmar
T1  - Maintaining protein stability of ∆Np63 via USP28 is required by squamous cancer cells
T2  - EMBO molecular medicine
N2  - The transcription factor ∆Np63 is a master regulator of epithelial cell identity and essential for the survival of squamous cell carcinoma (SCC) of lung, head and neck, oesophagus, cervix and skin. Here, we report that the deubiquitylase USP28 stabilizes ∆Np63 and maintains elevated ∆NP63 levels in SCC by counteracting its proteasome‐mediated degradation. Impaired USP28 activity, either genetically or pharmacologically, abrogates the transcriptional identity and suppresses growth and survival of human SCC cells. CRISPR/Cas9‐engineered in vivo mouse models establish that endogenous USP28 is strictly required for both induction and maintenance of lung SCC. Our data strongly suggest that targeting ∆Np63 abundance via inhibition of USP28 is a promising strategy for the treatment of SCC tumours.
KW  - ΔNp63
KW  - MYC
KW  - NOTCH
KW  - squamous cell carcinoma
KW  - USP28
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/56512
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-565128
SN  - 1757-4684
SN  - 1757-4676
VL  - 12
IS  - e11101
PB  - EMBO Press
CY  - Heidelberg
ER  -