Cristian Prieto García, 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
- 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.
Metadaten| Author: | Cristian Prieto GarcíaORCiDGND, Oliver Hartmann, Michaela ReisslandORCiD, Fabian Braun, Thomas Fischer, Susanne Walz, Christina Schülein‐Völk, Ursula Eilers, Carsten P. Ade, Marco A. CalzadoORCiD, Amir Orian, Hans-Michael Maric, Christian MünchORCiD, Mathias Rosenfeldt, Martin EilersORCiDGND, Markus Elmar DiefenbacherORCiD |
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| URN: | urn:nbn:de:hebis:30:3-565128 |
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| DOI: | https://doi.org/10.15252/emmm.201911101 |
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| ISSN: | 1757-4684 |
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| ISSN: | 1757-4676 |
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| Parent Title (German): | EMBO molecular medicine |
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| Publisher: | EMBO Press |
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| Place of publication: | Heidelberg |
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| Document Type: | Article |
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| Language: | English |
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| Date of Publication (online): | 2020/03/04 |
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| Date of first Publication: | 2020/03/04 |
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| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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| Release Date: | 2020/12/01 |
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| Tag: | MYC; NOTCH; USP28; squamous cell carcinoma; ΔNp63 |
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| Volume: | 12 |
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| Issue: | e11101 |
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| Page Number: | 25 |
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| HeBIS-PPN: | 476944163 |
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| Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
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| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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| Sammlungen: | Universitätspublikationen |
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| Licence (German): |  Creative Commons - Namensnennung 4.0 |
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