ArticleThe Journal of biological chemistry2010
p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 863 papers.
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Who cites it
863 citing papers in PubMed, 1,449 citations in OpenAlex.
- Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026Review
- Cysteine-based molecular switches: a focus on KEAP1 and BACH1 in regulating the antioxidant response.Archives of toxicology · 2026Review
- The interplay between vitamin D3 and Nrf2 signaling: mechanistic insights and therapeutic potentials.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Crosstalk Between Nrf2 and Metabolic Pathways: Redox Regulation, Glutaminolysis, and Cellular Proliferation.Cell biochemistry and biophysics · 2026Review
- A quantitative redox proteome of the human muscle response to exercise.bioRxiv : the preprint server for biology · 2026Article
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- Nrf2 as a therapeutic target of ginseng: A comprehensive review from preclinical evidence to clinical applications.Journal of ginseng research · 2026Review
- UBE2N flips the switch on for mitophagy and off for MASH.Nature metabolism · 2026Article
- p62/SQSTM1-KEAP1 complex prevents clearance of ubiquitinated Z alpha-1 antitrypsin and aggravates liver proteotoxicity.The Journal of biological chemistry · 2026Article
- Dose-dependent effect of curcumin nanomicelle on autophagy signaling in testis; a study on normal Wistar rats.Molecular biology reports · 2026Article
- Grape Seed Extract as an Adjuvant Therapy for Huntington Disease; A Narrative Review of Biological Plausibility and Potential Clinical Outcomes.Molecules (Basel, Switzerland) · 2026Review
- Microglia maintain retinal redox homeostasis following ablation of rod photoreceptors in zebrafish.The Journal of biological chemistry · 2026Article
- Ceramide kinase/ceramide 1-phosphate signaling regulates LC3B expression and autophagosome formation.Journal of lipid research · 2026Article
- Inhibition of SIK2 and SIK3 induces adaptive ER-phagy and creates a therapeutic vulnerability in ovarian cancer.Research square · 2026Article
- Alternol-Induced Oxidative Modification of SQSTM1/p62 Is Associated with Nrf2 Signaling and Autophagy-Related Responses in Prostate Cancer Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- A decline in skeletal muscle NOX4 abrogates exercise-induced adaptive homeostasis and exacerbates biological aging.Science advances · 2026Article
- Grape Seed Proanthocyanidins Enhance Time-Dependent HO-1 Activation and Improve Redox Homeostasis in Obesity-Induced Hepatic Dysfunction.Antioxidants (Basel, Switzerland) · 2026Article
- The SQSTM1/Animals : an open access journal from MDPI · 2026Article
803 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The p62/SQSTM1 (sequestosome 1) protein, which acts as a cargo receptor for autophagic degradation of ubiquitinated targets, is up-regulated by various stressors. Induction of the p62 gene by oxidative stress is mediated by NF-E2-related factor 2 (NRF2) and, at the same time, p62 protein contributes to the activation of NRF2, but hitherto the mechanisms involved were not known. Herein, we have mapped an antioxidant response element (ARE) in the p62 promoter that is responsible for its induction by oxidative stress via NRF2. Chromatin immunoprecipitation and gel mobility-shift assays verified that NRF2 binds to this cis-element in vivo and in vitro. Also, p62 docks directly onto the Kelch-repeat domain of Kelch-like ECH-associated protein 1 (KEAP1), via a motif designated the KEAP1 interacting region (KIR), thereby blocking binding between KEAP1 and NRF2 that leads to ubiquitylation and degradation of the transcription factor. The KIR motif in p62 is located immediately C-terminal to the LC3-interacting region (LIR) and resembles the ETGE motif utilized by NRF2 for its interaction with KEAP1. KIR is required for p62 to stabilize NRF2, and inhibition of KEAP1 by p62 occurs from a cytoplasmic location within the cell. The LIR and KIR motifs cannot be engaged simultaneously by LC3 and KEAP1, but because p62 is polymeric the interaction between KEAP1 and p62 leads to accumulation of KEAP1 in p62 bodies, which is followed by autophagic degradation of KEAP1. Our data explain how p62 contributes to activation of NRF2 target genes in response to oxidative stress through creating a positive feedback loop.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.