FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2023598683> ?p ?o ?g. }

• W2023598683 endingPage "22591" @default.
• W2023598683 startingPage "22576" @default.
• W2023598683 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. 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." @default.
• W2023598683 created "2016-06-24" @default.
• W2023598683 creator A5006599556 @default.
• W2023598683 creator A5014466375 @default.
• W2023598683 creator A5026735650 @default.
• W2023598683 creator A5035924475 @default.
• W2023598683 creator A5046024649 @default.
• W2023598683 creator A5054748771 @default.
• W2023598683 creator A5065056256 @default.
• W2023598683 creator A5076764844 @default.
• W2023598683 creator A5088634151 @default.
• W2023598683 date "2010-07-01" @default.
• W2023598683 modified "2023-10-17" @default.
• W2023598683 title "p62/SQSTM1 Is a Target Gene for Transcription Factor NRF2 and Creates a Positive Feedback Loop by Inducing Antioxidant Response Element-driven Gene Transcription" @default.
• W2023598683 cites W1935140087 @default.
• W2023598683 cites W1964716294 @default.
• W2023598683 cites W1967108243 @default.
• W2023598683 cites W1974437991 @default.
• W2023598683 cites W1975293376 @default.
• W2023598683 cites W1976578056 @default.
• W2023598683 cites W1981648285 @default.
• W2023598683 cites W1981912182 @default.
• W2023598683 cites W1987432765 @default.
• W2023598683 cites W1991005777 @default.
• W2023598683 cites W1991530716 @default.
• W2023598683 cites W1994823455 @default.
• W2023598683 cites W1995042437 @default.
• W2023598683 cites W1995771017 @default.
• W2023598683 cites W1997112179 @default.
• W2023598683 cites W2002061608 @default.
• W2023598683 cites W2002288000 @default.
• W2023598683 cites W2007339775 @default.
• W2023598683 cites W2008344420 @default.
• W2023598683 cites W2014918593 @default.
• W2023598683 cites W2015392958 @default.
• W2023598683 cites W2015703878 @default.
• W2023598683 cites W2022325384 @default.
• W2023598683 cites W2026938943 @default.
• W2023598683 cites W2033056129 @default.
• W2023598683 cites W2035239007 @default.
• W2023598683 cites W2038693622 @default.
• W2023598683 cites W2040114786 @default.
• W2023598683 cites W2043335299 @default.
• W2023598683 cites W2045965817 @default.
• W2023598683 cites W2047882425 @default.
• W2023598683 cites W2076935230 @default.
• W2023598683 cites W2078427707 @default.
• W2023598683 cites W2080155284 @default.
• W2023598683 cites W2080952734 @default.
• W2023598683 cites W2084644507 @default.
• W2023598683 cites W2085442981 @default.
• W2023598683 cites W2089519022 @default.
• W2023598683 cites W2091820232 @default.
• W2023598683 cites W2098257571 @default.
• W2023598683 cites W2101871553 @default.
• W2023598683 cites W2102354517 @default.
• W2023598683 cites W2110933512 @default.
• W2023598683 cites W2113027976 @default.
• W2023598683 cites W2119080788 @default.
• W2023598683 cites W2119399459 @default.
• W2023598683 cites W2119544175 @default.
• W2023598683 cites W2120480388 @default.
• W2023598683 cites W2122210284 @default.
• W2023598683 cites W2125123150 @default.
• W2023598683 cites W2130029858 @default.
• W2023598683 cites W2134703818 @default.
• W2023598683 cites W2137817444 @default.
• W2023598683 cites W2141755885 @default.
• W2023598683 cites W2141982524 @default.
• W2023598683 cites W2144103349 @default.
• W2023598683 cites W2145149844 @default.
• W2023598683 cites W2146124002 @default.
• W2023598683 cites W2146558971 @default.
• W2023598683 cites W2147984935 @default.
• W2023598683 cites W2155324869 @default.
• W2023598683 cites W2159820690 @default.
• W2023598683 cites W2171218310 @default.
• W2023598683 doi "https://doi.org/10.1074/jbc.m110.118976" @default.
• W2023598683 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2903417" @default.
• W2023598683 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20452972" @default.
• W2023598683 hasPublicationYear "2010" @default.
• W2023598683 type Work @default.
• W2023598683 sameAs 2023598683 @default.
• W2023598683 citedByCount "1136" @default.
• W2023598683 countsByYear W20235986832012 @default.
• W2023598683 countsByYear W20235986832013 @default.
• W2023598683 countsByYear W20235986832014 @default.
• W2023598683 countsByYear W20235986832015 @default.
• W2023598683 countsByYear W20235986832016 @default.
• W2023598683 countsByYear W20235986832017 @default.
• W2023598683 countsByYear W20235986832018 @default.
• W2023598683 countsByYear W20235986832019 @default.
• W2023598683 countsByYear W20235986832020 @default.
• W2023598683 countsByYear W20235986832021 @default.
• W2023598683 countsByYear W20235986832022 @default.
• W2023598683 countsByYear W20235986832023 @default.
• W2023598683 crossrefType "journal-article" @default.
• W2023598683 hasAuthorship W2023598683A5006599556 @default.

• next