RRC ID 46265
著者 Barna J, Princz A, Kosztelnik M, Hargitai B, Takács-Vellai K, Vellai T.
タイトル Heat shock factor-1 intertwines insulin/IGF-1, TGF-β and cGMP signaling to control development and aging.
ジャーナル BMC Dev Biol
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-β (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-β and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-β 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.
巻・号 12
ページ 32
公開日 2012-11-1
DOI 10.1186/1471-213X-12-32
PII 1471-213X-12-32
PMID 23116063
PMC PMC3558376
MeSH Aging / genetics Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cyclic GMP / metabolism* Cytochrome P-450 Enzyme System / metabolism Heat-Shock Response / genetics Insulin / metabolism Insulin-Like Growth Factor I / metabolism* Longevity / genetics RNA Interference RNA, Small Interfering Signal Transduction Stress, Physiological Transcription Factors / genetics Transcription Factors / metabolism* Transforming Growth Factor beta / metabolism* Up-Regulation
IF 2.0
引用数 25
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
線虫 tm4607