This leads to increased tumor progression, metastasis and therapy resistance in cancer, making Nrf2 an attractive therapeutic target. In this case, the proteasomal degradation of Nrf2 is suppressed by genetic alterations in Nrf2 and Keap1, but also by oncogenes such as KRASG12D or BRAFV619E, and the protective functions of the resulting gene products are exploited for the metabolization of chemotherapeutic agents or for the defense against radicals produced as a result of radiation therapy. Overactivation of Nrf2 has also been observed in tumor cells. The versatile cytoprotective properties of the Keap1/Nrf2 pathway serve as a protective function against diseases underlying oxidative stress or inflammatory mechanisms. This allows for a multifaceted cellular response to endogenous and exogenous oxidative stress that ensures maintenance of homeostasis. Those genes encode a variety of enzymes involved in the metabolism of protein degradation and the regulation of inflammatory responses such as Peroxiredoxin-1 (PRDX1), glutathione S-transferase (GST) and multidrug resistance-associated protein 1 (MRP). Nrf2 is a central component of the cellular detoxification machinery and mediates the transcription of approximately 250 genes. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) belongs to the cap’n’collar (CNC) basic-region leucine zipper (bZIP) transcription factor family and consists of a total of seven domains. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. BMBF 01GS08104, 01ZX1303C), the Deutsche Forschungsgemeinschaft (DFG), the German federal state North Rhine Westphalia (NRW) and the European Union (European Regional Development Fund: Invest In Your Future) (EFRE-800400), NEGECA (PerMed NRW) and EMODI. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the paper and its Supporting Information files.įunding: This work was co funded by the German Federal ministry for Education and Research (NGFNPlus and e:Med) (Grant No. Received: JanuAccepted: ApPublished: June 22, 2022Ĭopyright: © 2022 Wiedemann et al. PLoS ONE 17(6):Įditor: Alessio Lodola, University of Parma, ITALY (2022) Design and synthesis of Nrf2-derived hydrocarbon stapled peptides for the disruption of protein-DNA-interactions. Citation: Wiedemann B, Kamps D, Depta L, Weisner J, Cvetreznik J, Tomassi S, et al.