Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer.

ABSTRACT:

Background

Nuclear factor erythroid-2 related factor 2 (NRF2) is a redox-sensitive transcription factor that positively regulates the expression of genes encoding antioxidants, xenobiotic detoxification enzymes, and drug efflux pumps, and confers cytoprotection against oxidative stress and xenobiotics in normal cells. Kelch-like ECH-associated protein 1 (KEAP1) negatively regulates NRF2 activity by targeting it to proteasomal degradation. Increased expression of cellular antioxidants and xenobiotic detoxification enzymes has been implicated in resistance of tumor cells against chemotherapeutic drugs.

Methods and findings

Here we report a systematic analysis of the KEAP1 genomic locus in lung cancer patients and cell lines that revealed deletion, insertion, and missense mutat

SUBMITTER: Singh A 

PROVIDER: S-EPMC1584412 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature