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Dongjie Fan, Shunan Cao, Qiming Zhou, You Zhang, Lei Yue, Chang Han, Bo Yang, Yu Wang, Zhuo Ma, Lingxiang Zhu, Chuanpeng Liu
Trigger factor (TF) is a key component of the prokaryotic chaperone network, which is involved in many basic cellular processes, such as protein folding, protein trafficking, and ribosome assembly. The major chaperone site of TF has a cradle-like structure in which protein substrate may fold without interference from other proteins. Here, we investigated in vivo and in vitro the roles of hydrophobic and charged patches on the edge and interior of cradle during TF-assisted protein folding. Our results showed that most of the surface of the cradle was involved in TF-assisted protein folding, which was larger than found in early studies...
June 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Emmanuelle Gouot, Wajid Bhat, Anne Rufiange, Eric Fournier, Eric Paquet, Amine Nourani
CK2 is an essential protein kinase implicated in various cellular processes. In this study, we address a potential role of this kinase in chromatin modulations associated with transcription. We found that CK2 depletion from yeast cells leads to replication-independent increase of histone H3K56 acetylation and global activation of H3 turnover in coding regions. This suggests a positive role of CK2 in maintenance/recycling of the histone H3/H4 tetramers during transcription. Interestingly, strand-specific RNA-seq analyses show that CK2 inhibits global cryptic promoters driving both sense and antisense transcription...
June 14, 2018: Nucleic Acids Research
Patrick Rosendahl Andreassen, Jens Sivkær Pettersen, Mateusz Szczerba, Poul Valentin-Hansen, Jakob Møller-Jensen, Mikkel Girke Jørgensen
Production of curli, extracellular protein structures important for Escherichia coli biofilm formation, is governed by a highly complex regulatory mechanism that integrates multiple environmental signals through the involvement of numerous proteins and small non-coding RNAs (sRNAs). No less than seven sRNAs (McaS, RprA, GcvB, RydC, RybB, OmrA and OmrB) are known to repress the expression of the curli activator CsgD. Many of the sRNAs repress CsgD production by binding to the csgD mRNA at sites far upstream of the ribosomal binding site...
June 14, 2018: Nucleic Acids Research
Ivan Corbeski, Klemen Dolinar, Hans Wienk, Rolf Boelens, Hugo van Ingen
Genome replication, transcription and repair require the assembly/disassembly of the nucleosome. Histone chaperones are regulators of this process by preventing formation of non-nucleosomal histone-DNA complexes. Aprataxin and polynucleotide kinase like factor (APLF) is a non-homologous end-joining (NHEJ) DNA repair factor that possesses histone chaperone activity in its acidic domain (APLFAD). Here, we studied the molecular basis of this activity using biochemical and structural methods. We find that APLFAD is intrinsically disordered and binds histone complexes (H3-H4)2 and H2A-H2B specifically and with high affinity...
June 14, 2018: Nucleic Acids Research
Dustin K Goncharoff, Zhiqiang Du, Liming Li
Prion and prion-like phenomena are involved in the pathology of numerous human neurodegenerative diseases. The budding yeast, Saccharomyces cerevisiae, has a number of endogenous yeast prions-epigenetic elements that are transmitted as altered protein conformations and often manifested as heritable phenotypic traits. One such yeast prion, [SWI+], was discovered and characterized by our laboratory. The protein determinant of [SWI+], Swi1 was found to contain an amino-terminal, asparagine-rich prion domain. Normally, Swi1 functions as part of the SWI/SNF chromatin remodeling complex, thus, acting as a global transcriptional regulator...
September 1, 2018: FEMS Yeast Research
María I Herrera, Lucas D Udovin, Nicolás Toro-Urrego, Carlos F Kusnier, Juan P Luaces, Matilde Otero-Losada, Francisco Capani
Metabolic syndrome (MetS) is a cluster of risk factors that lead to microvascular dysfunction and chronic cerebral hypoperfusion (CCH). Long-standing reduction in oxygen and energy supply leads to brain hypoxia and protein misfolding, thereby linking CCH to Alzheimer's disease. Protein misfolding results in neurodegeneration as revealed by studying different experimental models of CCH. Regulating proteostasis network through pathways like the unfolded protein response (UPR), the ubiquitin-proteasome system (UPS), chaperone-mediated autophagy (CMA), and macroautophagy emerges as a novel target for neuroprotection...
2018: Frontiers in Neuroscience
Francesca Graziano, C Caruso Bavisotto, A Marino Gammazza, Francesca Rappa, Everly Conway de Macario, Albert J L Macario, Francesco Cappello, Claudia Campanella, Rosario Maugeri, Domenico Gerardo Iacopino
The European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada Phase III trial has validated as a current regimen for high-grade gliomas (HGG) a maximal safe surgical resection followed by radiotherapy with concurrent temozolamide. However, it is essential to balance maximal tumor resection with preservation of the patient’s neurological functions. Important developments in the fields of pre-operative and intra-operative neuro-imaging and neuro-monitoring have ameliorated the survival rate and the quality of life for patients affected by HGG...
June 14, 2018: Brain Sciences
Amanda R Wasylishen, Jeannelyn S Estrella, Vinod Pant, Gilda P Chau, Guillermina Lozano
Mutations in the death domain-associated protein (DAXX) have been recently identified in a substantial proportion of human pancreatic neuroendocrine tumors (PanNETs). Remarkably, however, little is known about the physiological role(s) of DAXX despite in vitro studies suggesting potential functions. Most prominently, and supported by tumor sequencing data, DAXX functions in concert with alpha thalassemia/mental retardation X-linked (ATRX) as a histone chaperone complex for the H3.3 variant. Studies have also identified potential roles in apoptosis, transcription, and negative regulation of the p53 tumor suppressor pathway...
June 14, 2018: Molecular Cancer Research: MCR
Li Zhang, Xian Cheng, Shichen Xu, Jiandong Bao, Huixin Yu
BACKGROUND: Thyroid cancer is the most common endocrine tumor. Our previous studies have demonstrated that curcumin can induce apoptosis in human papillary thyroid carcinoma BCPAP cells. However, the underlined mechanism has not been clearly elucidated. Endoplasmic reticulum (ER) is a major organelle for synthesis, maturation, and folding proteins as well as a large store for Ca. Overcoming chronically activated ER stress by triggering pro-apoptotic pathways of the unfolded protein response (UPR) is a novel strategy for cancer therapeutics...
June 2018: Medicine (Baltimore)
Jie-Ling Lai, Dong-Jie Tang, Yu-Wei Liang, Ren Zhang, Qi Chen, Zhen-Ping Qin, Zhen-Hua Ming, Ji-Liang Tang
The RNA chaperone, Hfq, is known to play extensive roles in bacterial growth and development. More recently, it has been shown to be required for virulence in many human and animal bacterial pathogens. Despite these studies little is known about the role Hfq plays in phytopathogenic bacteria. In this study, we show Hfq is required for full virulence of the crucifer black rot pathogen Xanthomonas campestris pv. campestris (Xcc). We demonstrate that an Xcc hfq deletion strain is highly attenuated for virulence in Chinese radish and shows a severe defect in the production of virulence factors including extracellular enzymes and extracellular polysaccharide...
June 14, 2018: Environmental Microbiology Reports
Kuan Chai, Xuerao Ning, Thảo Thi Thanh Nguyễn, Boya Zhong, Takao Morinaga, Zhihan Li, Masato Shingyoji, Yuji Tada, Koichiro Tatsumi, Hideaki Shimada, Kenzo Hiroshima, Naoto Yamaguchi, Masatoshi Tagawa
Heat shock protein 90 (HSP90) inhibitors suppressed MDM4 functions which mediated p53 ubiquitination, and blocked a chaperon function which influenced expression of the client proteins. We examined cytotoxic effects of the inhibitors, 17-allylamino-17-demetheoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG), on mesothelioma and investigated combinatory effects of the inhibitors and adenoviruses expressing the wild-type p53 gene (Ad-p53). A majority of mesothelioma lacks p14 and p16 expression, which leads to defective p53 pathway despite bearing the wild-type p53 genotype...
May 25, 2018: Oncotarget
Ranajay Saha, Samuel Verbanic, Irene A Chen
The organization of molecules into cells is believed to have been critical for the emergence of living systems. Early protocells likely consisted of RNA functioning inside vesicles made of simple lipids. However, little is known about how encapsulation would affect the activity and folding of RNA. Here we find that confinement of the malachite green RNA aptamer inside fatty acid vesicles increases binding affinity and locally stabilizes the bound conformation of the RNA. The vesicle effectively 'chaperones' the aptamer, consistent with an excluded volume mechanism due to confinement...
June 13, 2018: Nature Communications
Ya-Ju Sung, Ting-Yu Kao, Cheng-Liang Kuo, Chi-Chen Fan, An Ning Cheng, Wei-Cheng Fang, Han-Yu Chou, Yu-Kang Lo, Chung-Hsing Chen, Shih Sheng Jiang, I-Shou Chang, Chun-Hua Hsu, Jin-Ching Lee, Alan Yueh-Luen Lee
Mitochondrial Lon is a multi-function matrix protease with chaperone activity. However, little literature has been undertaken into detailed investigations on how Lon regulates apoptosis through its chaperone activity. Accumulating evidences indicate that various stresses induce transportation of p53 to mitochondria and activate apoptosis in a transcription-independent manner. Here we found that increased Lon interacts with p53 in mitochondrial matrix and restrains the apoptosis induced by p53 under oxidative stress by rescuing the loss of mitochondrial membrane potential (Δψm) and the release of cytochrome C and SMAC/Diablo...
June 13, 2018: Cell Death & Disease
Min Lu, Xiangwei He
Distinct chromatin organization features, such as centromeres and heterochromatin domains, are inherited epigenetically. However, the mechanisms that modulate the accuracy of epigenetic inheritance, especially at the individual nucleosome level, are not well understood. Here, using ChIP and next-generation sequencing (ChIP-Seq), we characterized Ccp1, a homolog of the histone chaperone Vps75 in budding yeast that functions in centromere chromatin duplication and heterochromatin maintenance in fission yeast (Schizosaccharomyces pombe)...
June 13, 2018: Journal of Biological Chemistry
Sonja Kroschwald, Matthias C Munder, Shovamayee Maharana, Titus M Franzmann, Doris Richter, Martine Ruer, Anthony A Hyman, Simon Alberti
How cells adapt to varying environmental conditions is largely unknown. Here, we show that, in budding yeast, the RNA-binding and stress granule protein Pub1 has an intrinsic property to form condensates upon starvation or heat stress and that condensate formation is associated with cell-cycle arrest. Release from arrest coincides with condensate dissolution, which takes minutes (starvation) or hours (heat shock). In vitro reconstitution reveals that the different dissolution rates of starvation- and heat-induced condensates are due to their different material properties: starvation-induced Pub1 condensates form by liquid-liquid demixing and subsequently convert into reversible gel-like particles; heat-induced condensates are more solid-like and require chaperones for disaggregation...
June 12, 2018: Cell Reports
Baomei Wang, Zhaoxia Li, Qijun Ran, Peng Li, Zhenghua Peng, Juren Zhang
ZmNF-YB16 is a basic NF-YB superfamily member and a member of a transcription factor complex composed of NF-YA, NF-YB, and NF-YC in maize. ZmNF-YB16 was transformed into the inbred maize line B104 to produce homozygous overexpression lines. ZmNF-YB16 overexpression improves dehydration and drought stress resistance in maize plants during vegetative and reproductive stages by maintaining higher photosynthesis and increases the maize grain yield under normal and drought stress conditions. Based on the examination of differentially expressed genes between the wild-type (WT) and transgenic lines by quantitative real time PCR (qRT-PCR), ZmNF-YB16 overexpression increased the expression of genes encoding antioxidant enzymes, the antioxidant synthase, and molecular chaperones associated with the endoplasmic reticulum (ER) stress response, and improved protection mechanism for photosynthesis system II...
2018: Frontiers in Plant Science
Mingjuan Yan, Shaoqun Shu, Chunyuan Guo, Chengyuan Tang, Zheng Dong
Acute kidney injury is a medical condition characterized by kidney damage with a rapid decline of renal function, which is associated with high mortality and morbidity. Recent research has further established an intimate relationship between acute kidney injury and chronic kidney disease. Perturbations of kidney cells in acute kidney injury result in the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum, leading to unfolded protein response or endoplasmic reticulum stress. In this review, we analyze the role and regulation of endoplasmic reticulum stress in acute kidney injury triggered by renal ischemia-reperfusion and cisplatin nephrotoxicity...
June 12, 2018: Annals of Medicine
Bruno G Aguiar, Prasad K Padmanabhan, Carole Dumas, Barbara Papadopoulou
VCP/p97/Cdc48 is one of the best-characterized type II cytosolic AAA+ ATPases most known for their role in ubiquitin-dependent protein quality control. Here, we provide functional insights into the role of the Leishmania VCP/p97 homolog (LiVCP) in the parasite intracellular development. We demonstrate that although LiVCP is an essential gene, L. infantum promastigotes can grow with less VCP. In contrast, growth of axenic and intracellular amastigotes is dramatically affected upon decreased LiVCP levels in heterozygous and temperature sensitive LiVCP mutants or the expression of dominant negative mutants known to specifically target the second conserved VCP ATPase domain, a major contributor of the VCP overall ATPase activity...
June 12, 2018: Cellular Microbiology
B B Gengenbach, C R Müschen, J F Buyel
Cardiovascular diseases are a prevalent cause of morbidity and mortality especially in industrialized countries. The human phosphatase and actin regulator 1 (PHACTR1) may be involved in such diseases, but its precise regulatory function remains unclear due to the large number of potential interaction partners. The same phenomenon makes this protein difficult to express in mammalian cells, but it is also an intrinsically disordered protein that likely aggregates when expressed in bacteria due to the absence of chaperones...
June 9, 2018: Protein Expression and Purification
Weihua Jin, Shuai Li, Jiale Chen, Bing Liu, Jie Li, Xueliang Li, Fuming Zhang, Robert J Linhardt, Weihong Zhong
Heparan sulfate (HS), is a glycosaminoglycan (GAG) involved in various biological processes, including blood coagulation, wound healing and embryonic development. HS 3-O-sulfotransferases (3-OST), which transfer the sulfo group to the 3-hydroxyl group of certain glucosamine residues, is a key enzyme in the biosynthesis of a number of biologically important HS chains. The 3-OST-1 isoform is one of the 7 known 3-OST isoforms and is important for the biosynthesis of anticoagulant HS chains. In this study, we cloned 3-OST-1 from the rat brain by reverse transcription-polymerase chain reaction (RT-PCR)...
June 9, 2018: Protein Expression and Purification
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