Publication: Maintaining protein stability of ∆Np63 via USP28 is required by squamous cancer cells.
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Identifiers
Date
2020-02-05
Authors
Prieto-Garcia, Cristian
Hartmann, Oliver
Reissland, Michaela
Braun, Fabian
Fischer, Thomas
Walz, Susanne
Schülein-Völk, Christina
Eilers, Ursula
Ade, Carsten P
Calzado, Marco A
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
EMBO Press
Abstract
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.
Description
MeSH Terms
Animals
Carcinoma, squamous cell
Epithelial cells
Humans
Mice
Protein stability
Trans-activators
Transcription factors
Tumor suppressor proteins
Ubiquitin thiolesterase
Carcinoma, squamous cell
Epithelial cells
Humans
Mice
Protein stability
Trans-activators
Transcription factors
Tumor suppressor proteins
Ubiquitin thiolesterase
DeCS Terms
Carcinoma de células escamosas
Células epiteliales
Estabilidad proteica
Factores de transcripción
Proteínas supresoras de tumor
Transactivadores
Células epiteliales
Estabilidad proteica
Factores de transcripción
Proteínas supresoras de tumor
Transactivadores
CIE Terms
Keywords
MYC, NOTCH, USP28, Squamous cell carcinoma, ∆Np63
Citation
Prieto-Garcia C, Hartmann O, Reissland M, Braun F, Fischer T, Walz S, et al. Maintaining protein stability of ∆Np63 via USP28 is required by squamous cancer cells. EMBO Mol Med. 2020 Apr 7;12(4):e11101