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Proteostasis: where do YOU work on the network?
What is Proteostasis?
Protein homeostasis or ‘proteostasis’ is the process that regulates proteins within the cell in order to maintain the health of both the cellular proteome and the organism itself. As such, the process is central to cell development, as well as working to ameliorate the rigours of cellular ageing and protecting cells against disease. Proteostasis does not involve just a single pathway or process but is maintained by a highly inter-connected network comprising many complex pathways that control, inter alia, the synthesis, folding, trafficking, aggregation, disaggregation, and degradation of proteins. In other words, the proteostasis network governs and controls the life path of a protein from birth to death.
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Synthesis, folding and unfolding
Aggregation & Disaggregation
Heat Shock Response
Oxidative Stress Response
Unfolded Protein Response
Post translational modifications
Protein Acetylation
Protein Methylation
Protein Phosphorylation
Protein Ubiquitinylation & SUMOylation
The Proteostasis Network
The proteostasis network encompasses events such as transcription and translation, folding and aggregation and disaggregation, trafficking, and autophagy and degradation. The complexity of such an interactive and connected network may be seen in the figure below. Proteostasis involves not just protein quality control but the combination of protein folding energetics and the adjustable proteostasis network capacity in order to optimally support cellular function. The network is additionally adjusted by signalling pathways, such as the heat shock response (HSR), the unfolded protein response (UPR), the oxidative stress response (OSR), and the ubiquitin-proteasome system (UPS), as these pathways mesh protein function with changing cellular and organismal needs.
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Key Proteostasis References
Selected literature
ProteoStat® Aggresome Detection Kit for flow cytometry and fluorescence microscopy
Heat Shock Proteins & the Cellular Stress Response Catalog
Cyto-ID™ Autophagy Detection Kit
Current Proteostasis Research Articles
2010 References
- A cellular perspective on conformational disease: the role of genetic background and proteostasis networks. Curr.Opin.Struct.Biol. 2010, PubMed
- A DNAJB chaperone subfamily with HDAC-dependent activities suppresses toxic protein aggregation. Mol.Cell 2010, PubMed
- An examination of alpha B-crystallin as a modifier of SOD1 aggregate pathology and toxicity in models of familial amyotrophic lateral sclerosis. J.Neurochem. 2010, PubMed
- ATP-independent reversal of a membrane protein aggregate by a chloroplast SRP subunit. Nat.Struct.Mol.Biol. 2010, PubMed
2009 References
- A kinetic assessment of the C. elegans amyloid disaggregation activity enables uncoupling of disassembly and proteolysis. Protein Sci. 2009, PubMed
- A small molecule inhibitor of inducible heat shock protein 70. Mol.Cell 2009, PubMed
- Angelman syndrome scientific symposium on the structure and function of UBE3A/E6AP. J.Child Neurol. 2009, PubMed
- Autophagy and ethanol-induced liver injury. World J.Gastroenterol. 2009, PubMed
2008 References
- A therapeutic dose of doxorubicin activates ubiquitin-proteasome system-mediated proteolysis by acting on both the ubiquitination apparatus and proteasome. Am.J.Physiol Heart Circ.Physiol 2008, PubMed
- Altered surfactant protein A gene expression and protein homeostasis in rats with emphysematous changes. Chin Med.J.(Engl.) 2008, PubMed
- Calcium sensitivity and cooperativity of permeabilized rat mesenteric lymphatics. Am.J.Physiol Regul.Integr.Comp Physiol 2008, PubMed
- Chemical and biological folding contribute to temperature-sensitive DeltaF508 CFTR trafficking. Traffic. 2008, PubMed
