Prieto-Garcia, CristianHartmann, OliverReissland, MichaelaBraun, FabianFischer, ThomasWalz, SusanneSchülein-Völk, ChristinaEilers, UrsulaAde, Carsten PCalzado, Marco AOrian, AmirMaric, Hans MMünch, ChristianRosenfeldt, MathiasEilers, MartinDiefenbacher, Markus E2023-02-082023-02-082020-02-05Prieto-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):e11101http://hdl.handle.net/10668/15197The 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/MYCNOTCHUSP28Squamous cell carcinoma∆Np63AnimalsCarcinoma, squamous cellEpithelial cellsHumansMiceProtein stabilityTrans-activatorsTranscription factorsTumor suppressor proteinsUbiquitin thiolesteraseresearch article32128997open accessCarcinoma de células escamosasCélulas epitelialesEstabilidad proteicaFactores de transcripciónProteínas supresoras de tumorTransactivadores10.15252/emmm.2019111011757-4684PMC7136964https://europepmc.org/articles/pmc7136964?pdf=renderhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136964/pdf