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Author

Jun Sun

Bio: Jun Sun is an academic researcher from Cornell University. The author has contributed to research in topics: CDC37 & Hsp33. The author has an hindex of 1, co-authored 1 publications receiving 48 citations.

Papers
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Journal ArticleDOI
TL;DR: It is demonstrated that cells distinguish moderate reductions in protein quality from severe protein misfolding using molecular chaperones to differentially regulate mTORC1 signaling, and the tight linkage between protein quality and quantity control provides a plausible mechanism coupling protein mis folding with metabolic dyshomeostasis.

50 citations


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Journal ArticleDOI
TL;DR: Since sirtuins are crucial to pathways that counter the decline in health that accompanies aging, pharmacological agents that boost sirtuin activity have clinical potential in treatment of diabetes, cardiovascular disease, dementia, osteoporosis, arthritis, and other conditions.

342 citations

Journal ArticleDOI
TL;DR: The molecular mechanisms that link ageing to main stress response pathways are surveyed, and how each pathway contributes to modulate the ageing process is discussed.
Abstract: Ageing is driven by the inexorable and stochastic accumulation of damage in biomolecules vital for proper cellular function. Although this process is fundamentally haphazard and uncontrollable, senescent decline and ageing is broadly influenced by genetic and extrinsic factors. Numerous gene mutations and treatments have been shown to extend the lifespan of diverse organisms ranging from the unicellular Saccharomyces cerevisiae to primates. It is becoming increasingly apparent that most such interventions ultimately interface with cellular stress response mechanisms, suggesting that longevity is intimately related to the ability of the organism to effectively cope with both intrinsic and extrinsic stress. Here, we survey the molecular mechanisms that link ageing to main stress response pathways, and mediate age‐related changes in the effectiveness of the response to stress. We also discuss how each pathway contributes to modulate the ageing process. A better understanding of the dynamics and reciprocal interplay between stress responses and ageing is critical for the development of novel therapeutic strategies that exploit endogenous stress combat pathways against age‐associated pathologies.

267 citations

Journal ArticleDOI
TL;DR: It is reported that intracellular proteotoxic stress reduces global protein synthesis by halting ribosomes on transcripts during elongation, suggesting a dual role of molecular chaperones in facilitating polypeptide elongation and cotranslational folding.

244 citations

Journal ArticleDOI
TL;DR: This work will address how protein homeostasis (proteostasis) is achieved at the level of the cell and organism, and how the threshold of the stress response is set to detect and combat protein misfolding.
Abstract: Organisms survive changes in the environmentbyaltering their rates of metabolism, growth, and reproduction. At the same time, the system must ensure the stabilityand functionalityof its macromolecules. Fluctuations in the environment are sensed by highly conserved stress responses and homeostatic mechanisms, and of these, the heat shock response (HSR) represents an essential response to acute and chronic proteotoxic damage. However, unlike the strategies employed to maintain the integrity of the genome, protection of the proteome mustbetailoredtoaccommodatethenormalfluxofnonnativeproteinsandthedifferencesin protein composition between cells, and among individuals. Moreover, adult cells are likely to have significant differences in the rates of synthesis and clearance that are influenced by intrinsicerrorsinproteinexpression,geneticpolymorphisms,andfluctuationsinphysiological and environmental conditions. Here, we will address how protein homeostasis (proteostasis) is achieved at the level of the cell and organism, and how the threshold of the stress response is set to detect and combat protein misfolding. For metazoans, the requirement forcoordinated function and growth imposes additional constraints on the detection, signaling,andresponsetomisfolding,andrequiresthattheHSRisintegratedintovariousaspectsof organismal physiology, such as lifespan. This is achieved by hierarchical regulation of heat shock factor 1 (HSF1) by the metabolic state of the cell and centralized neuronal control that could allow optimal resource allocation between cells and tissues. We will examine how protein folding quality control mechanisms in individual cells may be integrated into a multicellular level of control, and further, even custom-designed to support individual variability and impose additional constraints on evolutionary adaptation.

237 citations

Journal ArticleDOI
TL;DR: It is suggested that autophagy serves as a pathway for the turnover of ER membrane and its contents in response to ER stress in plants.
Abstract: In this article, we show that the endoplasmic reticulum (ER) in Arabidopsis thaliana undergoes morphological changes in structure during ER stress that can be attributed to autophagy. ER stress agents trigger autophagy as demonstrated by increased production of autophagosomes. In response to ER stress, a soluble ER marker localizes to autophagosomes and accumulates in the vacuole upon inhibition of vacuolar proteases. Membrane lamellae decorated with ribosomes were observed inside autophagic bodies, demonstrating that portions of the ER are delivered to the vacuole by autophagy during ER stress. In addition, an ER stress sensor, INOSITOL-REQUIRING ENZYME-1b (IRE1b), was found to be required for ER stress–induced autophagy. However, the IRE1b splicing target, bZIP60, did not seem to be involved, suggesting the existence of an undiscovered signaling pathway to regulate ER stress–induced autophagy in plants. Together, these results suggest that autophagy serves as a pathway for the turnover of ER membrane and its contents in response to ER stress in plants.

230 citations