PALB2 Interacts with KEAP1 To Promote NRF2 Nuclear Accumulation and Function
Copyright policy )PALB2 Interacts with KEAP1 To Promote NRF2 Nuclear Accumulation and Function
PALB2/FANCN is mutated in breast and pancreatic cancers and Fanconi anemia (FA). It controls the intranuclear localization, stability, and DNA repair function of BRCA2 and links BRCA1 and BRCA2 in DNA homologous recombination repair and breast cancer suppression. Here, we show that PALB2 directly interacts with KEAP1, an oxidative stress sensor that binds and represses the master antioxidant transcription factor NRF2. PALB2 shares with NRF2 a highly conserved ETGE-type KEAP1 binding motif and can effectively compete with NRF2 for KEAP1 binding. PALB2 promotes NRF2 accumulation and function in the nucleus and lowers the cellular reactive oxygen species (ROS) level. In addition, PALB2 also regulates the rate of NRF2 export from the nucleus following induction. Our findings identify PALB2 as a regulator of cellular redox homeostasis and provide a new link between oxidative stress and the development of cancer and FA.
- University of Arizona United States
- Centre national de la recherche scientifique France
- Institute of Human Genetics France
- Institut des Sciences Biologiques France
- University of Medicine and Dentistry of New Jersey United States
Cell Nucleus, Kelch-Like ECH-Associated Protein 1, DNA Repair, NF-E2-Related Factor 2, Tumor Suppressor Proteins, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Oxidative Stress, Cell Transformation, Neoplastic, Cell Line, Tumor, Neoplasms, Humans, Fanconi Anemia Complementation Group N Protein, Reactive Oxygen Species, Oxidation-Reduction, Protein Binding
Cell Nucleus, Kelch-Like ECH-Associated Protein 1, DNA Repair, NF-E2-Related Factor 2, Tumor Suppressor Proteins, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Oxidative Stress, Cell Transformation, Neoplastic, Cell Line, Tumor, Neoplasms, Humans, Fanconi Anemia Complementation Group N Protein, Reactive Oxygen Species, Oxidation-Reduction, Protein Binding
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