| Literature DB >> 22265419 |
Wei-Chung Chiang1, Tsui-Ting Ching, Hee Chul Lee, Carol Mousigian, Ao-Lin Hsu.
Abstract
Extended longevity is often correlated with increased resistance against various stressors. Insulin/IGF-1-like signaling (IIS) is known to have a conserved role in aging and cellular mechanisms against stress. In C. elegans, genetic studies suggest that heat-shock transcription factor HSF-1 is required for IIS to modulate longevity. Here, we report that the activity of HSF-1 is regulated by IIS. This regulation occurs at an early step of HSF-1 activation via two HSF-1 regulators, DDL-1 and DDL-2. Inhibition of DDL-1/2 increases longevity and thermotolerance in an hsf-1-dependent manner. Furthermore, biochemical analyses suggest that DDL-1/2 negatively regulate HSF-1 activity by forming a protein complex with HSF-1. The formation of this complex (DHIC) is affected by the phosphorylation status of DDL-1. Both the formation of DHIC and the phosphorylation of DDL-1 are controlled by IIS. Our findings point to DDL-1/2 as a link between IIS and the HSF-1 pathway.Entities:
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Year: 2012 PMID： 22265419 PMCID： PMC3615449 DOI： 10.1016/j.cell.2011.12.019
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582