Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy.

By Yoshinobu Ichimura, S. Waguri, Yu-shin Sou, S. Kageyama, J. Hasegawa, Ryosuke Ishimura, Tetsuya Saito, Yinjie Yang, T. Kouno, T. Fukutomi and 10 more. Molecules and Cells, 2013

1,109 citations recorded by the source corpus.

Subfields: Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/42d3c03a9d3516621a1dc6549f415e128c5d3f6e

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Citations in the corpus

Mechanisms and disease consequences of nonalcoholic fatty liver disease (2021, background): “In response to autophagy, which is stimulated by oxidative stress, transcriptional activity of nuclear factor erythroid 2-related factor (NRF2) may be increased to generate an antioxidant response, which can promote survival not only of steatotic hepatocytes but also of tumor cells (Ichimura et al.,”
The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway (2020, background): “which further enhances its ability to compete with NRF2 for KEAP1 binding (Table 3) (146, 147).”
Oxidative stress and autophagy: the clash between damage and metabolic needs (2014, background): “model, p62 binds to aggregates of ubiquitylated proteins and increases its affinity for Keap1 when phosphorylated at Ser(351) (Figure 2).(84) This event induces Keap1 degradation via autophagy(85) and leaves Nrf2 free to accumulate and translocate in the nucleus.”
Autophagy in malignant transformation and cancer progression (2015, positive): “…feedforward loop, stemming from the autophagy-dependent degradation of kelch-like ECH-associated protein 1 (KEAP1, the major negative regulator of NRF2) (Taguchi et al , 2012; Bae et al , 2013), as well as from the NRF2-activating phosphorylation of p62 (Inami et al , 2011; Ichimura et al , 2013).”
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): “Direct regulation of Nrf2 by mTORC1—As described above, mTORC1 can increase Nrf2 protein levels and induce its target genes because it phosphorylates Ser-351 in p62/SQSTM1, thereby enabling p62/SQSTM1 to bind to Keap1 and repress CRLKeap1 activity by promoting Keap1 degradation via autophagy [277].”
Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism (2016, background): “Moreover, phosphorylation of p62 at Ser(351) increases its binding affinity for Keap1, leading to the increased expression of cytoprotective Nrf2 targets [170].”
p62 links autophagy and Nrf2 signaling. (2015, background): “To date, however, the kinase responsible for p62 phosphorylation at S351 has not been identi-fied [34].”
p62 links the autophagy pathway and the ubiqutin–proteasome system upon ubiquitinated protein degradation (2016, positive): “The S351 of KIR is phosphorylated, leading to a rising affinity of p62 for Keap1 and followed by sequestration of Keap1 on the cargoes [75].”