RT Journal Article
T1 Maintaining protein stability of ∆Np63 via USP28 is required by squamous cancer cells.
A1 Prieto-Garcia, Cristian
A1 Hartmann, Oliver
A1 Reissland, Michaela
A1 Braun, Fabian
A1 Fischer, Thomas
A1 Walz, Susanne
A1 Schülein-Völk, Christina
A1 Eilers, Ursula
A1 Ade, Carsten P
A1 Calzado, Marco A
A1 Orian, Amir
A1 Maric, Hans M
A1 Münch, Christian
A1 Rosenfeldt, Mathias
A1 Eilers, Martin
A1 Diefenbacher, Markus E
K1 MYC
K1 NOTCH
K1 USP28
K1 Squamous cell carcinoma
K1 ∆Np63
AB 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.
PB EMBO Press
YR 2020
FD 2020-02-05
LK http://hdl.handle.net/10668/15197
UL http://hdl.handle.net/10668/15197
LA en
NO 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
NO We are grateful to the animal facility and Barbara Bauer at the Biocenter,University Würzburg. C.P.G. and O.H. are supported by the German Cancer Aid via grant 70112491, M.E. is supported by the TransOnc priority programme of the German Cancer Aid within grant 70112951 (ENABLE), and M.R. is funded by the DFG-GRK 2243 and IZKF B335. M.E.D. and A.O. are funded by the GermanIsraeli Foundation grant 1431. T. F. is funded by the IZKF programme Z2/CS-1.
DS RISalud
RD Apr 9, 2025