PALB2 interacts with KEAP1 to promote NRF2 nuclear accumulation and function

Jianglin Ma, Hong Cai, Tongde Wu, Bijan Sobhian, Yanying Huo, Allen Alcivar, Monal Mehta, Ka Lung Cheung, Shridar Ganesan, Ah Ng Tony Kong, Donna D. Zhang, Bing Xia

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1506-1517
Number of pages12
JournalMolecular and cellular biology
Volume32
Issue number8
DOIs
StatePublished - Apr 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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