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

Loading...
Thumbnail Image

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
Metrics
Google Scholar
Export

Research Projects

Organizational Units

Journal Issue

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

DeCS Terms

Carcinoma de células escamosas
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