@article{SchueleinVoelkWolfZhuetal.2014,
  author    = {Sch{\"u}lein-V{\"o}lk, Christina and Wolf, Elmar and Zhu, Jing and Xu, Wenshan and Taranets, Lyudmyla and Hellmann, Andreas and J{\"a}nicke, Laura A. and Diefenbacher, Markus E. and Behrens, Axel and Eilers, Martin and Popov, Nikita},
  title     = {Dual Regulation of Fbw7 Function and Oncogenic Transformation by Usp28},
  series = {CELL REPORTS},
  volume    = {9},
  journal   = {CELL REPORTS},
  number    = {3},
  issn      = {2211-1247},
  doi       = {10.1016/j.celrep.2014.09.057},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118219},
  pages     = {1099-1109},
  year      = {2014},
  abstract  = {Fbw7, the substrate recognition subunit of SCF(Fbw7) ubiquitin ligase, mediates the turnover of multiple proto-oncoproteins and promotes its own degradation. Fbw7-dependent substrate ubiquitination is antagonized by the Usp28 deubiquitinase. Here, we show that Usp28 preferentially antagonizes autocatalytic ubiquitination and stabilizes Fbw7, resulting in dose-dependent effects in Usp28 knockout mice. Monoallelic deletion of Usp28 maintains stable Fbw7 but drives Fbw7 substrate degradation. In contrast, complete knockout triggers Fbw7 degradation and leads to the accumulation of Fbw7 substrates in several tissues and embryonic fibroblasts. On the other hand, overexpression of Usp28 stabilizes both Fbw7 and its substrates. Consequently, both complete loss and ectopic expression of Usp28 promote Ras-driven oncogenic transformation. We propose that dual regulation of Fbw7 activity by Usp28 is a safeguard mechanism for maintaining physiological levels of proto-oncogenic Fbw7 substrates, which is equivalently disrupted by loss or overexpression of Usp28.},
  language  = {en}
}
@article{Prieto‐GarciaHartmannReisslandetal.2020,
  author    = {Prieto-Garcia, Cristian and Hartmann, Oliver and Reissland, Michaela and Braun, Fabian and Fischer, Thomas and Walz, Susanne and Sch{\"u}lein-V{\"o}lk, Christina and Eilers, Ursula and Ade, Carsten P. and Calzado, Marco A. and Orian, Amir and Maric, Hans M. and M{\"u}nch, Christian and Rosenfeldt, Mathias and Eilers, Martin and Diefenbacher, Markus E.},
  title     = {Maintaining protein stability of ∆Np63 via USP28 is required by squamous cancer cells},
  series = {EMBO Molecular Medicine},
  volume    = {12},
  journal   = {EMBO Molecular Medicine},
  number    = {4},
  doi       = {10.15252/emmm.201911101},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218303},
  year      = {2020},
  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.},
  language  = {en}
}