Keap1 Recruits Neh2 through Binding to ETGE and DLG Motifs: Characterization of the Two-Site Molecular Recognition Model

By K. I. Tong, Y. Katoh, H. Kusunoki, K. Itoh, Toshiyuki Tanaka, Masayuki Yamamoto. Molecular and Cellular Biology, 2006

735 citations recorded by the source corpus.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/30ed3b65479803c8e3a52efa8210a20ced022a5a

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Citations in the corpus

Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution (2011, methodology): “These observations contributed to the ‘hinge and latch model’ (Tong et al. 2006b).”
The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway (2020, background): “reported for the shorter DLG motif (Table 3) (91, 98).”
Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy (2008, background): “The double glycine repeat and the C-terminal region of Keap1 (hereafter refer as to Keap1-DC) recognize both the DLG and ETGE motifs of Nrf2 (20, 21).”
Transcriptional Regulation by Nrf2 (2017, background): “The Neh2 domain contains two highly conserved amino acid stretches, the DLG and ETGE motifs, which mediate the interaction with Nrf2 negative regulator Kelch-like ECH-associated protein 1 (Keap1) and seven lysine residues targeted for ubiquitylation and subsequent proteasomal degradation of Nrf2 (60”
Molecular Mechanisms of Nrf2-Mediated Antioxidant Response (2009, background): “It is very interesting to observe that in this nine-turns a-helix, six of seven lysine residues are located on the same side [55].”
Role of nrf2 in oxidative stress and toxicity. (2013, background): “In this two-site-binding, or hinge-and-latch, model (49) (Figure 2c), Keap1 recruits newly synthesized Nrf2 by binding to Neh2.”
A Noncanonical Mechanism of Nrf2 Activation by Autophagy Deficiency: Direct Interaction between Keap1 and p62 (2010, background): “Binding of both the DLG and ETGE motifs of Nrf2 to the Kelch domain of a Keap1 homodimer is essential in presenting the lysine residues of Nrf2 in the correct orientation to accept ubiquitin (14, 22, 30).”
p62 links autophagy and Nrf2 signaling. (2015, background): “According to the hinge and latch model, the ETGE motif has a higher affinity for Keap1 than the DLG motif, which causes the latter to dynamically associate and dissociate from Keap1 to generate oscillating “closed” (associated) and “open” (dissociated) conformations [29–33].”
Activation of Nrf2-antioxidant signaling attenuates NF-κB-inflammatory response and elicits apoptosis (2008, background): “, a high affinity phase I binding, mediated by the ETGE motif and a low affinity phase II binding mediated by the DLG motif, has been distinguished [8].”
ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis (2007, background): “Zinc coordination by Cys residues in KeaP1 is reminiscent of Hsp33 and Rsra, suggesting that, in a similar way to 103,131 .”
Direct interaction between Nrf2 and p21(Cip1/WAF1) upregulates the Nrf2-mediated antioxidant response. (2009, background): “It is believed that the Keap1 homodimer binds both the 29 DLG and 79 ETGE motifs in Nrf2 to align the seven ubiquitin-accepting lysine residues between these motifs into a conformation suitable for ubiquitin conjugation (McMahon et al., 2006; Tong et al., 2006, 2007; Zhang et al., 2004).”