2017
DOI: 10.1074/jbc.r117.800169
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Abstract: Edited by Ruma BanerjeeTranscription factor Nrf2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. Nrf2 induces the expression of detoxification and antioxidant enzymes and suppresses the induction of pro-inflammatory cytokine genes. Keap1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of Cullin 3-based E3 ubiquitin ligase. Keap1 regulates the activity of Nrf2 and acts as a sensor for oxidative and electrophilic stresses. In this review, we discus… Show more

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Cited by 312 publications
(256 citation statements)
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“…Specifically, we demonstrate that TLR stimulation in dendritic cells induces the Keap1-mediated antioxidant response in an RNI-dependent manner (Figure 2) and that Keap1 knockdown or small-molecule inhibition of the Keap1-Nrf2 interaction was sufficient to inhibit TLR-driven cytokine production (Figure 4). These findings provide mechanistic insight into recent studies evaluating the role of Keap1 and Nrf2 in models of pathological inflammation (Suzuki and Yamamoto, 2017). Induction of Nrf2 by systemic Keap1 knockdown ameliorated autoimmune symptoms in Treg-deficient Scurfy mice (Suzuki et al, 2017).…”
Section: Discussionsupporting
confidence: 57%
“…Specifically, we demonstrate that TLR stimulation in dendritic cells induces the Keap1-mediated antioxidant response in an RNI-dependent manner (Figure 2) and that Keap1 knockdown or small-molecule inhibition of the Keap1-Nrf2 interaction was sufficient to inhibit TLR-driven cytokine production (Figure 4). These findings provide mechanistic insight into recent studies evaluating the role of Keap1 and Nrf2 in models of pathological inflammation (Suzuki and Yamamoto, 2017). Induction of Nrf2 by systemic Keap1 knockdown ameliorated autoimmune symptoms in Treg-deficient Scurfy mice (Suzuki et al, 2017).…”
Section: Discussionsupporting
confidence: 57%
“…The functional ARE has been defined as TMANNRTGACT-CAGCRWWWW, where M = A or C, R = A or G and W = A or T (9). It is important to recognize that Nrf2 not only induces gene expression but also functions as a suppressor of gene expression (e.g., pro-inflammatory gene expression) (12). …”
Section: Introductionmentioning
confidence: 99%
“…Oxidative and electrophilic stresses that modify critical cysteine residues cause a conformational change in Keap1 that abrogates Keap1’s ability to direct Nrf2’s ubiquitination [reviewed in refs. (12,19, 20)]. In addition to stress-related activation, a number of proteins [e.g., p21 (21), p62, PALB2, IKKB, DPP3 (22) and iASPP (23)] can competitively bind to Keap1 and inhibit Nrf2 ubiquitination.…”
Section: Introductionmentioning
confidence: 99%
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“…Mechanistically, Nrf2 is held in an inactive complex in the cytosol through interaction with its negative regulator, Kelch‐like ECH‐associated protein 1 (Keap1), where it undergoes ubiquitination and subsequent turnover by the proteasome through interaction with Keap1 and Cullin3. Alternatively, in response to oxidative stress, Keap1 undergoes oxidative modification and Nrf2 is released from Keap1 50. Nrf2 then translocates into the nucleus where together with a small‐molecule regulator Maf1, it binds to antioxidant response elements (ARE) in the promoter region of key antioxidant genes.…”
Section: Diabetes and Cardiovascular Diseasementioning
confidence: 99%