| Title: | "Heat shock factor-1 intertwines insulin/IGF-1, TGF-beta and cGMP signaling to control development and aging" |
| Author(s): | Barna J; Princz A; Kosztelnik M; Hargitai B; Takacs-Vellai K; Vellai T; |
| Address: | "Department of Genetics, Eotvos Lorand University, Budapest, Hungary" |
| ISSN/ISBN: | 1471-213X (Electronic) 1471-213X (Linking) |
| Abstract: | "BACKGROUND: Temperature affects virtually all cellular processes. A quick increase in temperature challenges the cells to undergo a heat shock response to maintain cellular homeostasis. Heat shock factor-1 (HSF-1) functions as a major player in this response as it activates the transcription of genes coding for molecular chaperones (also called heat shock proteins) that maintain structural integrity of proteins. However, the mechanisms by which HSF-1 adjusts fundamental cellular processes such as growth, proliferation, differentiation and aging to the ambient temperature remain largely unknown. RESULTS: We demonstrate here that in Caenorhabditis elegans HSF-1 represses the expression of daf-7 encoding a TGF-beta (transforming growth factor-beta) ligand, to induce young larvae to enter the dauer stage, a developmentally arrested, non-feeding, highly stress-resistant, long-lived larval form triggered by crowding and starvation. Under favorable conditions, HSF-1 is inhibited by crowding pheromone-sensitive guanylate cyclase/cGMP (cyclic guanosine monophosphate) and systemic nutrient-sensing insulin/IGF-1 (insulin-like growth factor-1) signaling; loss of HSF-1 activity allows DAF-7 to promote reproductive growth. Thus, HSF-1 interconnects the insulin/IGF-1, TGF-beta and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-beta pathway-interacting gene, daf-9/cytochrome P450, thereby fine-tuning the decision between normal growth and dauer formation. CONCLUSION: Together, these results provide mechanistic insight into how temperature, nutrient availability and population density coordinately influence development, lifespan, behavior and stress response through HSF-1" |
| Keywords: | Aging/genetics Animals Caenorhabditis elegans/genetics/*growth & development/*metabolism Caenorhabditis elegans Proteins/genetics/*metabolism Cyclic GMP/*metabolism Cytochrome P-450 Enzyme System/metabolism Heat-Shock Response/genetics Insulin/metabolism; |
| Notes: | "MedlineBarna, Janos Princz, Andrea Kosztelnik, Monika Hargitai, Balazs Takacs-Vellai, Krisztina Vellai, Tibor eng Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2012/11/03 BMC Dev Biol. 2012 Nov 1; 12:32. doi: 10.1186/1471-213X-12-32" |
