HSF-1 is a highly conserved transcription factor that plays a central role in protecting organisms from diverse cellular stresses.However,the mechanisms by which HSF-1 senses and responds to different types of stress ...HSF-1 is a highly conserved transcription factor that plays a central role in protecting organisms from diverse cellular stresses.However,the mechanisms by which HSF-1 senses and responds to different types of stress remain incompletely understood.COPIIcoated vesicles,responsible for transporting cargo from the endoplasmic reticulum to the Golgi apparatus,are essential for protein secretion and cellular homeostasis.Disruption of these vesicles impairs protein secretion and triggers severe proteotoxic stress.Here,we show that HSF-1 directly monitors COPII vesicle dysfunction through interactions with the core COPII component SEC-23,in both Caenorhabditis elegans and NIH3T3 cells.Inhibition of SEC-23 or SAR-1 disrupts COPII vesicle formation,leading to the release of HSF-1 from the COPII complex.This release induces a specific transcriptomic change to restore protein homeostasis.Our findings reveal a conserved mechanism by which HSF-1 responds to COPII vesicle dysregulation,providing new insights into the HSF-1-centered proteostasis network.展开更多
Alzheimer’s disease(AD)is a major public health concern worldwide and the few drugs currently available only treat the symptoms.Hence,there is a strong need to find more effective anti-AD agents.Cynanchum otophyllum ...Alzheimer’s disease(AD)is a major public health concern worldwide and the few drugs currently available only treat the symptoms.Hence,there is a strong need to find more effective anti-AD agents.Cynanchum otophyllum is a traditional Chinese medicine for treating epilepsy,and otophylloside B(Ot B),isolated from C.otophyllum,is the essential active component.Having previously identified anti-aging effects of Ot B,we evaluated Ot B for AD prevention in C.elegant models of AD and found that Ot B extended lifespan,increased heat stress-resistance,delayed body paralysis,and increased the chemotaxis response.Collectively,these results indicated thatOt B protects against Aβtoxicity.Further mechanistic studies revealed that Ot B decreased Aβdeposition by decreasing the expression of Aβat the mRNA level.Genetic analyses showed that Ot B mediated its effects by increasing the activity of heat shock transcription factor(HSF)by upregulating the expression of hsf-1 and its target genes,hsp-12.6,hsp-16.2 and hsp-70.Ot B also increased the expression of sod-3 by partially activating DAF-16,while SKN-1 was not essential in Ot B-mediated protection against Aβtoxicity.展开更多
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19000000)。
文摘HSF-1 is a highly conserved transcription factor that plays a central role in protecting organisms from diverse cellular stresses.However,the mechanisms by which HSF-1 senses and responds to different types of stress remain incompletely understood.COPIIcoated vesicles,responsible for transporting cargo from the endoplasmic reticulum to the Golgi apparatus,are essential for protein secretion and cellular homeostasis.Disruption of these vesicles impairs protein secretion and triggers severe proteotoxic stress.Here,we show that HSF-1 directly monitors COPII vesicle dysfunction through interactions with the core COPII component SEC-23,in both Caenorhabditis elegans and NIH3T3 cells.Inhibition of SEC-23 or SAR-1 disrupts COPII vesicle formation,leading to the release of HSF-1 from the COPII complex.This release induces a specific transcriptomic change to restore protein homeostasis.Our findings reveal a conserved mechanism by which HSF-1 responds to COPII vesicle dysregulation,providing new insights into the HSF-1-centered proteostasis network.
基金supported by the Natural Science Foundation of China(81671405,81370453)Natural Science Foundation of Yunnan province(2013FA045,2015FB172)Open Funds of Guangdong Key Laboratory of Marine Materia Mcdica(LMM2016-1).
文摘Alzheimer’s disease(AD)is a major public health concern worldwide and the few drugs currently available only treat the symptoms.Hence,there is a strong need to find more effective anti-AD agents.Cynanchum otophyllum is a traditional Chinese medicine for treating epilepsy,and otophylloside B(Ot B),isolated from C.otophyllum,is the essential active component.Having previously identified anti-aging effects of Ot B,we evaluated Ot B for AD prevention in C.elegant models of AD and found that Ot B extended lifespan,increased heat stress-resistance,delayed body paralysis,and increased the chemotaxis response.Collectively,these results indicated thatOt B protects against Aβtoxicity.Further mechanistic studies revealed that Ot B decreased Aβdeposition by decreasing the expression of Aβat the mRNA level.Genetic analyses showed that Ot B mediated its effects by increasing the activity of heat shock transcription factor(HSF)by upregulating the expression of hsf-1 and its target genes,hsp-12.6,hsp-16.2 and hsp-70.Ot B also increased the expression of sod-3 by partially activating DAF-16,while SKN-1 was not essential in Ot B-mediated protection against Aβtoxicity.
