Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer.

By B. Padmanabhan, K. I. Tong, T. Ohta, Y. Nakamura, Maria Scharlock, Makiko Ohtsuji, Moon-Il Kang, A. Kobayashi, S. Yokoyama, Masayuki Yamamoto. Molecules and Cells, 2006

744 citations recorded by the source corpus.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8bd9f106e202a3830f16d191baee53d608eb4bc3

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Citations in the corpus

The emerging role of the Nrf2–Keap1 signaling pathway in cancer (2013, background): “Gain-of-function mutations in NRF2 and loss-of-function mutations in KEAP1 and CUL3 have been identified in several human cancers (Padmanabhan et al. 2006; Singh et al. 2006; Nioi and Nguyen 2007; Ohta et al. 2008; Shibata et al. 2008a; Li et al. 2011; Ooi et al. 2013; Sato et al. 2013).”
Mechanistic Studies of the Nrf2-Keap1 Signaling Pathway (2006, background): “Recently, the crystal structure of the Kelch domain has been solved and revealed a six β-propeller structure (Li et al., 2004; Padmanabhan et al., 2006).”
The cytoprotective role of the Keap1–Nrf2 pathway (2011, methodology): “In total, 13 intermolecular interactions are formed between Keap1 and Nrf2 (Padmanabhan et al. 2006; Lo et al. 2006).”
The Dual Roles of NRF2 in Cancer. (2016, background): “The first somatic mutations in the NRF2 pathway were identified in the Kelch-like repeat domain of KEAP1 in two human lung adenocarcinoma cell lines [43].”
Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells (2011, background): “Recently, somatic mutations in Keap1 and Nrf2 were identified in lung, gall bladder, and head and neck tumors (Padmanabhan et al., 2006; Singh et al., 2006; Shibata et al., 2008a,b).”
Molecular Mechanisms of Nrf2-Mediated Antioxidant Response (2009, background): “When an ETGEcontaining peptide was co-crystallized with the Kelch domain, the ETGE-containing peptide assumed a U-shape conformation; two short anti-parallel b-strands were linked by two overlapping type I b-turns [64,65].”
The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1 (2010, background): “The CTR domain contributes to the structural fold of Keap1-DC, which is required for interaction with Nrf2 (ref”
Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease (2015, positive): “It was first reported that cell lines and tumors from patients with non-small-cell lung carcinoma contain somatic mutations that inactivate Keap1, thereby causing constitutive Nrf2 activation [249, 401].”
Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders (2010, neutral): “Whereas many aspects of the model are still controversial and the intricate details of the regulation of the pathway are not fully understood (200, 324, 345), there is voluminous experimental evidence for a mechanism of regulation of Keap1 activity through its reactive cysteine residues.”
PGC1α Expression Defines a Subset of Human Melanoma Tumors with Increased Mitochondrial Capacity and Resistance to Oxidative Stress (2013, positive): “by activating mutations in Nrf2 or through inactivating mutations in KEAP1 (an Nrf2 cytoplasmic repressor) (Padmanabhan et al., 2006; Singh et al., 2006; Shibata et al., 2008; Ohta et al., 2008).”
Role of nrf2 in oxidative stress and toxicity. (2013, background): “Neh2 interacts with Keap1 DC in a ratio of 1:2 through its ETGE and DLG motifs (43, 49, 50).”
Autophagy-deficient mice develop multiple liver tumors. (2011, result): “7) can be important for progression of tumors and is consistent with reports that somatic mutations in either Keap1 or Nrf2 that cause constitutive Nrf2 activation have been found in human cancers (Padmanabhan et al. 2006; Shibata et al. 2008).”