Authors: McColl, Gawain; Rogers, Aric N; Alavez, Silvestre; Hubbard, Alan E; Melov, Simon; Link, Christopher D; Bush, Ashley I; Kapahi, Pankaj; Lithgow, Gordon J
Abstract: The insulin-like signaling (ILS) pathway regulates metabolism and is known to modulate adult life span in C. elegans. Altered stress responses and resistance to a wide range of stressors are also associated with changes in ILS and contribute to enhanced longevity. The transcription factors DAF-16 and HSF-1 are key effectors of the longevity phenotype. We demonstrate that increased intrinsic thermotolerance, due to lower ILS, is not dependent on stress-induced transcriptional responses but instead requires active protein translation. Translation profiling experiments reveal genes that are posttranscriptionally regulated in response to altered ILS during heat shock in a DAF-16-dependent manner. Furthermore, several novel proteins are specifically required for ILS effects on thermotolerance. We propose that lowered ILS results in metabolic and physiological changes. These DAF-16-induced changes precondition a translational response under acute stress to modulate survival.
Keywords: Animals; Caenorhabditis elegans/genetics/*physiology; Caenorhabditis elegans Proteins/genetics/metabolism; Heat-Shock Proteins/genetics/metabolism; Hot Temperature; Insulin/*metabolism; Microarray Analysis; Promoter Regions, Genetic; RNA, Messenger/genetics/metabolism; Receptor, Insulin/genetics/metabolism; Recombinant Fusion Proteins/genetics/metabolism; Ribosomes/metabolism; Signal Transduction/*physiology; Stress, Physiological/*physiology; *Survival Rate; Transcription Factors/genetics/metabolism; *Transcription, Genetic|
Journal: Cell Metab Volume: 12 Issue: 3 Pages: 260-72 Date: Sept. 8, 2010 PMID: 20816092 |
McColl, Gawain, Rogers, Aric N, Alavez, Silvestre, Hubbard, Alan E, Melov, Simon, Link, Christopher D, Bush, Ashley I, Kapahi, Pankaj, Lithgow, Gordon J (2010) Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans. Cell Metab 12: 260-72.
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