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- W4328049394 endingPage "373" @default.
- W4328049394 startingPage "351" @default.
- W4328049394 abstract "Significance: Organisms adapt to changing environments by engaging cellular stress response pathways that serve to restore proteostasis and enhance survival. A primary adaptive mechanism is the integrated stress response (ISR), which features phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2). Four eIF2α kinases respond to different stresses, enabling cells to rapidly control translation to optimize management of resources and reprogram gene expression for stress adaptation. Phosphorylation of eIF2 blocks its guanine nucleotide exchange factor, eIF2B, thus lowering the levels of eIF2 bound to GTP that is required to deliver initiator transfer RNA (tRNA) to ribosomes. While bulk messenger RNA (mRNA) translation can be sharply lowered by heightened phosphorylation of eIF2α, there are other gene transcripts whose translation is unchanged or preferentially translated. Among the preferentially translated genes is ATF4, which directs transcription of adaptive genes in the ISR. Recent Advances and Critical Issues: This review focuses on how eIF2α kinases function as first responders of stress, the mechanisms by which eIF2α phosphorylation and other stress signals regulate the exchange activity of eIF2B, and the processes by which the ISR triggers differential mRNA translation. To illustrate the synergy between stress pathways, we describe the mechanisms and functional significance of communication between the ISR and another key regulator of translation, mammalian/mechanistic target of rapamycin complex 1 (mTORC1), during acute and chronic amino acid insufficiency. Finally, we discuss the pathological conditions that stem from aberrant regulation of the ISR, as well as therapeutic strategies targeting the ISR to alleviate disease. Future Directions: Important topics for future ISR research are strategies for modulating this stress pathway in disease conditions and drug development, molecular processes for differential translation and the coordinate regulation of GCN2 and other stress pathways during physiological and pathological conditions. Antioxid. Redox Signal. 39, 351–373." @default.
- W4328049394 created "2023-03-22" @default.
- W4328049394 creator A5018888344 @default.
- W4328049394 creator A5033878744 @default.
- W4328049394 creator A5082229689 @default.
- W4328049394 date "2023-08-01" @default.
- W4328049394 modified "2023-09-30" @default.
- W4328049394 title "Surviving and Adapting to Stress: Translational Control and the Integrated Stress Response" @default.
- W4328049394 cites W1505761263 @default.
- W4328049394 cites W1510407036 @default.
- W4328049394 cites W1531537331 @default.
- W4328049394 cites W1546139069 @default.
- W4328049394 cites W1831651395 @default.
- W4328049394 cites W1899601083 @default.
- W4328049394 cites W1924601622 @default.
- W4328049394 cites W1963688091 @default.
- W4328049394 cites W1964366152 @default.
- W4328049394 cites W1975091138 @default.
- W4328049394 cites W1976860224 @default.
- W4328049394 cites W1977603207 @default.
- W4328049394 cites W1977966865 @default.
- W4328049394 cites W1978510012 @default.
- W4328049394 cites W1980438612 @default.
- W4328049394 cites W1980626096 @default.
- W4328049394 cites W1981280480 @default.
- W4328049394 cites W1984426737 @default.
- W4328049394 cites W1988202801 @default.
- W4328049394 cites W1991017037 @default.
- W4328049394 cites W1991999080 @default.
- W4328049394 cites W2003924215 @default.
- W4328049394 cites W2005809131 @default.
- W4328049394 cites W2007080316 @default.
- W4328049394 cites W2009536847 @default.
- W4328049394 cites W2010581370 @default.
- W4328049394 cites W2011026076 @default.
- W4328049394 cites W2013317097 @default.
- W4328049394 cites W2013966205 @default.
- W4328049394 cites W2014194720 @default.
- W4328049394 cites W2014423141 @default.
- W4328049394 cites W2015803078 @default.
- W4328049394 cites W2016701287 @default.
- W4328049394 cites W2019425923 @default.
- W4328049394 cites W2023666553 @default.
- W4328049394 cites W2024407185 @default.
- W4328049394 cites W2024751967 @default.
- W4328049394 cites W2028279477 @default.
- W4328049394 cites W2028866472 @default.
- W4328049394 cites W2035692565 @default.
- W4328049394 cites W2046277983 @default.
- W4328049394 cites W2046278771 @default.
- W4328049394 cites W2047690919 @default.
- W4328049394 cites W2047887493 @default.
- W4328049394 cites W2048098925 @default.
- W4328049394 cites W2048551040 @default.
- W4328049394 cites W2056664023 @default.
- W4328049394 cites W2060428113 @default.
- W4328049394 cites W2061420374 @default.
- W4328049394 cites W2063385165 @default.
- W4328049394 cites W2064489767 @default.
- W4328049394 cites W2064813406 @default.
- W4328049394 cites W2065151741 @default.
- W4328049394 cites W2067018477 @default.
- W4328049394 cites W2067040999 @default.
- W4328049394 cites W2068335084 @default.
- W4328049394 cites W2068469924 @default.
- W4328049394 cites W2071849521 @default.
- W4328049394 cites W2074471441 @default.
- W4328049394 cites W2075739226 @default.
- W4328049394 cites W2077784911 @default.
- W4328049394 cites W2078061821 @default.
- W4328049394 cites W2079743290 @default.
- W4328049394 cites W2080448503 @default.
- W4328049394 cites W2081625427 @default.
- W4328049394 cites W2084952088 @default.
- W4328049394 cites W2086699218 @default.
- W4328049394 cites W2089787026 @default.
- W4328049394 cites W2097409962 @default.
- W4328049394 cites W2097634421 @default.
- W4328049394 cites W2098624952 @default.
- W4328049394 cites W2100472948 @default.
- W4328049394 cites W2102050179 @default.
- W4328049394 cites W2102528998 @default.
- W4328049394 cites W2103446696 @default.
- W4328049394 cites W2107106045 @default.
- W4328049394 cites W2109535551 @default.
- W4328049394 cites W2110420807 @default.
- W4328049394 cites W2111587627 @default.
- W4328049394 cites W2113286169 @default.
- W4328049394 cites W2115218339 @default.
- W4328049394 cites W2116654909 @default.
- W4328049394 cites W2119055716 @default.
- W4328049394 cites W2120736516 @default.
- W4328049394 cites W2122500419 @default.
- W4328049394 cites W2126859035 @default.
- W4328049394 cites W2127848114 @default.
- W4328049394 cites W2131632095 @default.
- W4328049394 cites W2132545724 @default.
- W4328049394 cites W2132729882 @default.