NFE2L2 and MAFG bind the SQSTM1 gene

Stable Identifier
Reaction [binding]
Homo sapiens
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SQSTM1, also known as p62, is a cytosolic receptor for proteins destined for autophagic degradation. SQSTM1 interacts with LC3 proteins through its LC3-interacting region (LIR) to deliver cargo to the forming autophagosome (reviewed in Lamark et al, 2017).
SQSTM1 gene expression is upregulated by various cellular stressors including oxidative stress. Upregulation of SQSTM1 in response to oxidative stress is mediated by the binding of a heterodimer of MAFG and NFE2L2 to the antioxidant response element (ARE) in the promoter (Jain et al, 2020).
SQSTM1 protein in turn regulates NFE2L2 levels by competing with NFE2L2 for binding to KEAP1. KEAP1 is part of a CUL3 ubiquitin ligase complex that targets NFE2L2 for degradation: by competing for binding with KEAP1, SQSTM1 stabilizes NFE2L2. This establishes a positive feedback loop enhancing both NFE2L2 and SQSTM1 protein levels (Jain et al, 2020).
Literature References
PubMed ID Title Journal Year
29233872 Regulation of selective autophagy: the p62/SQSTM1 paradigm

Svenning, S, Lamark, T, Johansen, T

Essays Biochem 2017
20452972 p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription

Larsen, KB, Sjøttem, E, Awuh, JA, Jain, A, Lamark, T, Hayes, JD, Johansen, T, McMahon, M, Øvervatn, A

J Biol Chem 2010
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