mTORC1 Links Protein Quality and Quantity Control by Sensing Chaperone Availability
TLDR
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.About:
This article is published in Journal of Biological Chemistry.The article was published on 2010-08-27 and is currently open access. It has received 50 citations till now. The article focuses on the topics: Hsp33 & Chaperone (protein).read more
Citations
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The ER Stress Inducer l-Azetidine-2-Carboxylic Acid Elevates the Levels of Phospho-eIF2α and of LC3-II in a Ca2+-Dependent Manner
Gemma Roest,Evelien Hesemans,Kirsten Welkenhuyzen,Tomas Luyten,Nikolai Engedal,Geert Bultynck,Jan B. Parys +6 more
TL;DR: The proline analogue l-azetidine-2-carboxylic acid was used to induce ER stress, and its effect on autophagy and Ca2+ homeostasis and it was deduced that activation of the PERK branch is required for the AZC-induced lipidation of LC3.
Journal ArticleDOI
Hepatic DNAJB9 Drives Anabolic Biasing to Reduce Steatosis and Obesity.
Fangfang Sun,Yilie Liao,Xingfan Qu,Xia Xiao,Shaocong Hou,Zheqin Chen,Haipeng Huang,Pingping Li,Suneng Fu +8 more
TL;DR: Restoration of hepatic DNAJB9 expression effectively improves insulin sensitivity, restores protein synthesis, and suppresses food intake, accompanied by reduced hepatic steatosis and adiposity in multiple mouse models of obesity.
Journal ArticleDOI
The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer
Weikun Qian,Ke Chen,Tao Qin,Ying Xiao,Jie Li,Yangyang Yue,Cancan Zhou,Jiguang Ma,Wanxing Duan,Jianjun Lei,Liang Han,Li Li,Xin Shen,Zheng Wu,Qingyong Ma,Zheng Wang +15 more
TL;DR: In this article, the authors found that pharmacological inhibition of heat shock factor 1 (HSF1) slowed pancreatic cancer initiation and suppressed the pancreatitis-induced formation of pancreatic precancerous lesion.
A systems biology perspective on the consequences of aneuploidy in human cells
TL;DR: The analysis shows that despite the variability in chromosome content, aneuploidy triggers uniform transcriptional response in human cells, which might represent novel biomarkers to assess the malignant potential of a tumor.
Heat Shock Gene Dysregulation and Inactivation of Drug Therapy
TL;DR: The success of the use of these chronic disease medications may require nutritional interventions that accelerate drug metabolism and improve insulin resistance and endocrine therapy associated with the delay in the pathogenesis of NAFLD.
References
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Journal ArticleDOI
TOR signaling in growth and metabolism.
TL;DR: The physiological consequences of mammalianTORC1 dysregulation suggest that inhibitors of mammalian TOR may be useful in the treatment of cancer, cardiovascular disease, autoimmunity, and metabolic disorders.
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Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
David E. Harrison,Randy Strong,Zelton D Sharp,James F. Nelson,Clinton M. Astle,Kevin Flurkey,Nancy L. Nadon,J. Erby Wilkinson,Krystyna Frenkel,Christy S. Carter,Christy S. Carter,Marco Pahor,Marco Pahor,Martin A. Javors,Elizabeth Fernandez,Richard A. Miller +15 more
TL;DR: It is reported that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age.
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mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex that Signals to the Cell Growth Machinery
Do Hyung Kim,Dos D. Sarbassov,Siraj M. Ali,Jessie E. King,Robert R. Latek,Hediye Erdjument-Bromage,Paul Tempst,David M. Sabatini +7 more
TL;DR: It is reported that mTOR forms a stoichiometric complex with raptor, an evolutionarily conserved protein with at least two roles in the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels.
Journal ArticleDOI
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
TL;DR: It is shown that TSC1–TSC2 inhibits the p70 ribosomal protein S6 kinase 1 and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation) and these functions are mediated by inhibition of the mammalian target of rapamycin (mTOR).
Journal ArticleDOI
Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.
Dos D. Sarbassov,Siraj M. Ali,Do Hyung Kim,David A. Guertin,Robert R. Latek,Hediye Erdjument-Bromage,Paul Tempst,David M. Sabatini +7 more
TL;DR: It is found that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals.