Keap1-resistant ΔN-Nrf2 isoform does not translocate to the nucleus upon electrophilic stress

• DOI: 10.1101/2022.06.10.495609
• Publication Date: 2022-06-10T16:10:21Z
• Authors: Sara Mikac; Alicja Dziadosz; Monikaben Padariya; Umesh Kalathiya; Robin Fahraeus; Natalia Marek-Trz...; Elżbieta Chruściel; Zuzanna Urban-Wój...; Ines Papak; Łukasz Arcimowicz; Tomasz Marjanski; Witold Rzyman; Alicja Sznarkowska
• Keywords: KEAP1; Derepression; Transcription

Abstract The Nrf2 pathway is an essential defense in a cell. It responds to oxidative and electrophilic stress via derepression of from Keap1-Cul3-mediated degradation, accumulation the nucleus transcriptional activation number detoxifying cell protective target genes. Here we report that normal cancer cells also express N-terminally truncated isoform (ΔN-Nrf2), which originates alternative promoter. Co-immunoprecipitation together with molecular dynamics simulation showed binding between ΔN-Nrf2 Keap1 impaired, resulting much higher stability this form. retained cytoplasm response stress, indicating it does not regulate transcription under same stimuli as full-length Nrf2. Altogether data suggests has other functions than genes, most probably rely on protein-protein interactions cytoplasm. regulation these takes place level transcription. Significance Statement This work signifies importance assigning function produced protein. transcripts second promoter gene give rise form upon thus different role regulation. resistant Keap1-Cul3 degradation highly expressed all tested types. points new, cytoplasmic cells, determined at