• BMB Reports
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• 제38권3호
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• pp.259-265
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• 2005

Proteins must fold into their correct three-dimensional conformation in order to attain their biological function. Conversely, protein aggregation and misfolding are primary contributors to many devastating human diseases, such as prion-mediated infections, Alzheimer's disease, type II diabetes and cystic fibrosis. While the native conformation of a polypeptide is encoded within its primary amino acid sequence and is sufficient for protein folding in vitro, the situation in vivo is more complex. Inside the cell, proteins are synthesized or folded continuously; a process that is greatly assisted by molecular chaperones. Molecular chaperones re a group of structurally diverse and mechanistically distinct proteins that either promote folding or prevent the aggregation of other proteins. With our increasing understanding of the proteome, it is becoming clear that the number of proteins that can be classified as molecular chaperones is increasing steadily. Many of these proteins have novel but essential cellular functions that differ from that of more 'conventional' chaperones, such as Hsp70 and the GroE system. This review focuses on the emerging role of molecular chaperones in protein quality control, i.e. the mechanism that rids the cell of misfolded or incompletely synthesized polypeptides that otherwise would interfere with normal cellular function.

• BMB Reports
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• 제45권1호
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• pp.1-6
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• 2012

Hsp90 is one of the most conserved molecular chaperones ubiquitously expressed in normal cells and over-expressed in cancer cells. A pool of Hsp90 was found in cancer mitochondria and the expression of the mitochondrial Hsp90 homolog, TRAP1, was also elevated in many cancers. The mitochondrial pool of chaperones plays important roles in regulating mitochondrial integrity, protecting against oxidative stress, and inhibiting cell death. Pharmacological inactivation of the chaperones induced mitochondrial dysfunction and concomitant cell death selectively in cancer cells, suggesting they can be target proteins for the development of cancer therapeutics. Several drug candidates targeting TRAP1 and Hsp90 in the mitochondria have been developed and have shown strong cytotoxic activity in many cancers, but not in normal cells in vitro and in vivo. In this review, recent developments in the study of mitochondrial chaperones and the mitochondria-targeted chaperone inhibitors are discussed.

• The Plant Pathology Journal
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• 제31권4호
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• pp.323-333
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• 2015

As sessile organisms, plants are exposed to persistently changing stresses and have to be able to interpret and respond to them. The stresses, drought, salinity, chemicals, cold and hot temperatures, and various pathogen attacks have interconnected effects on plants, resulting in the disruption of protein homeostasis. Maintenance of proteins in their functional native conformations and preventing aggregation of non-native proteins are important for cell survival under stress. Heat shock proteins (HSPs) functioning as molecular chaperones are the key components responsible for protein folding, assembly, translocation, and degradation under stress conditions and in many normal cellular processes. Plants respond to pathogen invasion using two different innate immune responses mediated by pattern recognition receptors (PRRs) or resistance (R) proteins. HSPs play an indispensable role as molecular chaperones in the quality control of plasma membrane-resident PRRs and intracellular R proteins against potential invaders. Here, we specifically discuss the functional involvement of cytosolic and endoplasmic reticulum (ER) HSPs/chaperones in plant immunity to obtain an integrated understanding of the immune responses in plant cells.

• Journal of Life Science
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• 제9권1호
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• pp.90-92
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• 1999

Deficient thyroglobulin is one of the important causes of congenital hypothyroid goiter with a prevalence of -1/40,000 humans. We now demonstrate that in cog/cog mice showing hypothyroidism, four endoplasmic reticulum-molecular chaperones stably bind to thyroglobulin, providing insight into physiologic regulation of endoplasmic reticulum storage diseases.

• BMB Reports
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• 제32권3호
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• pp.311-316
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• 1999

Studies in adipocytes indicate that secretion of active lipoprotein lipase (LPL) was strictly regulated by a quality control system in the endoplasmic reticulum (ER). However, there has been no report about the ER chaperones participating in the folding and assembly of LPL. Many chaperones are known to bind unfolded proteins and dissociate from them through the ATP-hydrolyzing reaction. In this study, putative ER chaperones for LPL were determined by affinity chromatography using denatured LPL as an affinity ligand and elution with ATP. BiP, grp94, calreticulin, and another 50 kDa K-D-E-L protein in the ER of rat adipose tissue were bound to denatured LPL and eluted by ATP. Calnexin was bound to denatured LPL; however, it was not eluted by ATP but by acetic acid. These results indicate that, at least, BiP, grp94, calreticulin, calnexin, and the unidentified 50 kDa protein might act as putative chaperones for the proper folding and assembly of LPL in ER.

• 생명과학회지
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• 제17권12호
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• pp.1760-1765
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• 2007

생명체 내에서 일어나는 거의 모든 반응은 단백질이 촉진하거나 수행한다. 단백질은 세포질과 소포체에서 합성될 때 엄격하게 조절된다. 그러나, 새로이 합성된 모든 단백질이 살아남아서 생명을 유지시키는 기능에 관여하게 되지는 않는다. 가장 알맞은 생리학적 in vitro 실험 조건에서 새로이 합성된 단백질의 약 3분의 1 정도는 합성되자마자 proteasome에 의해 빠르게 분해된다고 보고되었다. 또한, 단백질은 합성이 성공적으로 이루어진 이후에는 3차원 구조를 갖기 위해 접힘(folding)이 이루어져야 하고, subunit들은 assembly 과정을 거쳐야 비로소 성숙된 단백질로서 기능을 하게 된다. 어떤 단백질군은 자연적으로 접힘이 일어나는 반면 어떤 단백질군은 분자 샤페론(molecular chaperones)과 folding enzymes의 도움을 받아야만 접힘이 일어난다. 분자 샤페론은 세포 전역에 분포하고 있으며, 세균에서부터 고등 동식물에 이르기까지 모든 생명체에 존재한다. 이들 중 Hsp70군은 많이 연구된 분자 샤페론으로서 지난 10여년 동안 조절인자들이 새로이 발견되어 작용 mechanism이 보다 자세히 밝혀졌다. 본 총설에서 Hsp70군과 그 조절인자들에 대한 전반적인 서술을 하였으며, 이들의 기능이 분자 샤페론 기능 외에 생체 내에서 중요한 기능들이 새롭게 밝혀지고 있어 이들의 작용 mechanism을 조명함으로 이해를 돕고자 한다.

• 생물정신의학
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• 제14권4호
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• pp.221-231
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• 2007

Recent researches have shown that important cellular-based autoprotective mechanisms are mediated by heat-shock proteins(HSPs), also called 'molecular chaperones'. HSPs as molecular chaperones are the primary cellular defense mechanism against damage to the proteome, initiating refolding of denatured proteins and regulating degradation after severe protein damage. HSPs also modulate multiple events within apoptotic pathways to help sustain cell survival following damaging stimuli. HSPs are induced by almost every type of stresses including physical and psychological stresses. Our nervous system in the brain are more vulnerable to stress and damage than any other tissues due to HSPs insufficiency. The normal function of HSPs is a key factor for endogenous stress adaptation of neural tissues. HSPs play an important role in the process of neurodevelopment, neurodegeneration, and neuroendocrine regulation. The altered function of HSPs would be associated with the development of several neuropsychiatric disorders. Therefore, an understanding of HSPs activities could help to improve autoprotective mechanism of our neural system. This paper will review the literature related to the significance of HSPs in neuropsychiatric field.

• 대한의생명과학회지
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• 제14권1호
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• pp.59-62
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• 2008

This experiment was performed to study the effect of TSH (thyroid-stimulating hormone) on the expression of endoplasmic reticulum (ER) chaperones in the rat thyrocytes FRTL-5 cells. Although the expressions of ER membrane kinases (ATF6, IRE1 and PERK) were specially enhanced under absence of TSH, no remarkable up- or down regulations of ER chaperones (BiP, CHOP and Calnexin) were detected by TSH. We firstly report here that TSH by dose up-regulated expression of ER membrane kinases in FRTL-5 culture thyrocytes.

• BMB Reports
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• 제42권4호
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• pp.227-231
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• 2009

The eukaryotic genome forms a chromatin structure that contains repeating nucleosome structures. Nucleosome packaging is regulated by chromatin remodeling factors such as histone chaperones. The Saccharomyces cerevisiae H3/H4 histone chaperones, CAF-1 and Asf1, regulate DNA replication and chromatin assembly. CAF-1 function is largely restricted to non-transcriptional processes in heterochromatin, whereas Asf1 regulates transcription together with another H3/H4 chaperone, HIR. This study examined the role of the yeast H3/H4 histone chaperones, Asf1, HIR, and CAF-1 in chromatin dynamics during transcription. Unexpectedly, CAF-1 was recruited to the actively transcribed region in a similar way to HIR and Asf1. In addition, the three histone chaperones genetically interacted with Set2-dependent H3 K36 methylation. Similar to histone chaperones, Set2 was required for tolerance to excess histone H3 but not to excess H2A, suggesting that CAF-1, Asf1, HIR, and Set2 function in a related pathway and target chromatin during transcription.

• Mycobiology
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• 제43권3호
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• pp.272-279
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• 2015

To screen molecular chaperones similar to small heat shock proteins (sHsps), but without ${\alpha}$-crystalline domain, heat-stable proteins from Schizosaccharomyces pombe were analyzed by 2-dimensional electrophoresis and matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Sixteen proteins were identified, and four recombinant proteins, including cofilin, NTF2, pyridoxin biosynthesis protein (Snz1) and Wos2 that has an ${\alpha}$-crystalline domain, were purified. Among these proteins, only Snz1 showed the anti-aggregation activity against thermal denaturation of citrate synthase. However, pre-heating of NTF2 and Wos2 at $70^{\circ}C$ for 30 min, efficiently prevented thermal aggregation of citrate synthase. These results indicate that Snz1 and NTF2 possess molecular chaperone activity similar to sHsps, even though there is no ${\alpha}$-crystalline domain in their sequences.