Matches in SemOpenAlex for { <https://semopenalex.org/work/W4211235156> ?p ?o ?g. }
- W4211235156 endingPage "157" @default.
- W4211235156 startingPage "147" @default.
- W4211235156 abstract "Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of cellular homeostasis that controls the expression of more than 1% of human genes related to biotransformation reactions, redox homeostasis, energetic metabolism, DNA repair, and proteostasis. Its activity has a tremendous impact on physiology and pathology and therefore it is very tightly regulated, mainly at the level of protein stability. In addition to the very well established regulation by the ubiquitin E3 ligase adapter Keap1, recent advances have identified a novel mechanism based on signaling pathways that regulate glycogen synthase kinse-3 (GSK-3). This kinase phosphorylates specific serine residues in the Neh6 domain of Nrf2 to create a degradation domain that is then recognized by the ubiquitin ligase adapter β-TrCP and tagged for proteasome degradation by a Cullin1/Rbx1 complex. Here we review the mechanistic elements and the signaling pathways that participate in this regulation by GSK-3/β-TrCP. These pathways include those activated by ligands of tyrosine kinase, G protein-coupled, metabotropic, and ionotropic receptors that activate phosphatidyl inositol 3-kinase (PI3K)/ATK and by the canonical WNT signaling pathway, where a fraction of Nrf2 interacts with Axin1/GSK-3. Considering that free Nrf2 protein is localized in the nucleus, we propose a model termed double flux controller to explain how Keap1 and β-TrCP coordinate the stability of Nrf2 in several scenarios. The GSK-3/β-TrCP axis provides a novel therapeutic strategy to modulate Nrf2 activity." @default.
- W4211235156 created "2022-02-13" @default.
- W4211235156 creator A5067010957 @default.
- W4211235156 date "2015-11-01" @default.
- W4211235156 modified "2023-10-05" @default.
- W4211235156 title "Structural and functional characterization of Nrf2 degradation by glycogen synthase kinase 3/β-TrCP" @default.
- W4211235156 cites W1508475810 @default.
- W4211235156 cites W1531084694 @default.
- W4211235156 cites W1546972840 @default.
- W4211235156 cites W1566657518 @default.
- W4211235156 cites W1587164985 @default.
- W4211235156 cites W1758789982 @default.
- W4211235156 cites W1908612571 @default.
- W4211235156 cites W1963561816 @default.
- W4211235156 cites W1964918914 @default.
- W4211235156 cites W1965093955 @default.
- W4211235156 cites W1966034049 @default.
- W4211235156 cites W1966665720 @default.
- W4211235156 cites W1966830269 @default.
- W4211235156 cites W1973141016 @default.
- W4211235156 cites W1974016983 @default.
- W4211235156 cites W1974549459 @default.
- W4211235156 cites W1977736016 @default.
- W4211235156 cites W1978110337 @default.
- W4211235156 cites W1978714931 @default.
- W4211235156 cites W1980385765 @default.
- W4211235156 cites W1980739328 @default.
- W4211235156 cites W1982342854 @default.
- W4211235156 cites W1983316247 @default.
- W4211235156 cites W1984534635 @default.
- W4211235156 cites W1988593777 @default.
- W4211235156 cites W1990561391 @default.
- W4211235156 cites W1990686581 @default.
- W4211235156 cites W1991631628 @default.
- W4211235156 cites W1994242450 @default.
- W4211235156 cites W1995630168 @default.
- W4211235156 cites W1996521867 @default.
- W4211235156 cites W1998777048 @default.
- W4211235156 cites W1999148207 @default.
- W4211235156 cites W1999894132 @default.
- W4211235156 cites W2002019400 @default.
- W4211235156 cites W2004399117 @default.
- W4211235156 cites W2007267381 @default.
- W4211235156 cites W2013680091 @default.
- W4211235156 cites W2015928690 @default.
- W4211235156 cites W2017498511 @default.
- W4211235156 cites W2019835347 @default.
- W4211235156 cites W2020317656 @default.
- W4211235156 cites W2023514845 @default.
- W4211235156 cites W2024494094 @default.
- W4211235156 cites W2025286289 @default.
- W4211235156 cites W2025330029 @default.
- W4211235156 cites W2026873752 @default.
- W4211235156 cites W2027728353 @default.
- W4211235156 cites W2029102160 @default.
- W4211235156 cites W2030749349 @default.
- W4211235156 cites W2031757730 @default.
- W4211235156 cites W2033228162 @default.
- W4211235156 cites W2035376760 @default.
- W4211235156 cites W2035676834 @default.
- W4211235156 cites W2036246693 @default.
- W4211235156 cites W2038582574 @default.
- W4211235156 cites W2038612772 @default.
- W4211235156 cites W2044693162 @default.
- W4211235156 cites W2046312189 @default.
- W4211235156 cites W2050044704 @default.
- W4211235156 cites W2050892991 @default.
- W4211235156 cites W2052548231 @default.
- W4211235156 cites W2053047691 @default.
- W4211235156 cites W2053063855 @default.
- W4211235156 cites W2056583667 @default.
- W4211235156 cites W2056907950 @default.
- W4211235156 cites W2058138221 @default.
- W4211235156 cites W2064059449 @default.
- W4211235156 cites W2064634296 @default.
- W4211235156 cites W2068790240 @default.
- W4211235156 cites W2073447787 @default.
- W4211235156 cites W2073679813 @default.
- W4211235156 cites W2076405456 @default.
- W4211235156 cites W2076892771 @default.
- W4211235156 cites W2077895679 @default.
- W4211235156 cites W2078224613 @default.
- W4211235156 cites W2080671121 @default.
- W4211235156 cites W2080952734 @default.
- W4211235156 cites W2081985759 @default.
- W4211235156 cites W2083670406 @default.
- W4211235156 cites W2085201901 @default.
- W4211235156 cites W2087311397 @default.
- W4211235156 cites W2087330517 @default.
- W4211235156 cites W2087394121 @default.
- W4211235156 cites W2088614896 @default.
- W4211235156 cites W2091945251 @default.
- W4211235156 cites W2092261702 @default.
- W4211235156 cites W2094312617 @default.
- W4211235156 cites W2094661084 @default.
- W4211235156 cites W2096171021 @default.
- W4211235156 cites W2097634036 @default.
- W4211235156 cites W2099491441 @default.