Maintaining protein stability of ∆Np63 via USP28 is required by squamous cancer cells

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 t
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.
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Metadaten
Author:Cristian Prieto‐Garcia, Oliver Hartmann, Michaela Reissland, Fabian Braun, Thomas Fischer, Susanne Walz, Christina Schülein‐Völk, Ursula Eilers, Carsten P. Ade, Marco A. Calzado, Amir Orian, Hans-Michael Maric, Christian Münch, Mathias Rosenfeldt, Martin Eilers, Markus Elmar Diefenbacher
URN:urn:nbn:de:hebis:30:3-565128
DOI:http://dx.doi.org/10.15252/emmm.201911101
ISSN:1757-4684
ISSN:1757-4676
Parent Title (German):EMBO molecular medicine
Publisher:EMBO Press
Place of publication:Heidelberg
Document Type:Article
Language:English
Date of Publication (online):2020/03/04
Date of first Publication:2020/03/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/12/01
Tag:MYC; NOTCH; USP28; squamous cell carcinoma; ΔNp63
Volume:12
Issue:e11101
Pagenumber:25
HeBIS PPN:476944163
Institutes:Biochemie und Chemie
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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