Login / Signup

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

Cristian Prieto-GarciaOliver HartmannMichaela ReisslandFabian BraunThomas FischerSusanne WalzChristina Schülein-VölkUrsula EilersCarsten P AdeMarco A CalzadoAmir OrianHans M MaricChristian MünchMathias RosenfeldtMartin EilersMarkus Elmar Diefenbacher
Published in: EMBO molecular medicine (2020)
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.
Keyphrases