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https://www.readbyqxmd.com/read/28724966/acetylation-induced-tdp-43-pathology-is-suppressed-by-an-hsf1-dependent-chaperone-program
#1
Ping Wang, Connor M Wander, Chao-Xing Yuan, Michael S Bereman, Todd J Cohen
TDP-43 pathology marks a spectrum of multisystem proteinopathies including amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and sporadic inclusion body myositis. Surprisingly, it has been challenging to recapitulate this pathology, highlighting an incomplete understanding of TDP-43 regulatory mechanisms. Here we provide evidence supporting TDP-43 acetylation as a trigger for disease pathology. Using cultured cells and mouse skeletal muscle, we show that TDP-43 acetylation-mimics promote TDP-43 phosphorylation and ubiquitination, perturb mitochondria, and initiate degenerative inflammatory responses that resemble sporadic inclusion body myositis pathology...
July 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28724629/abrogation-of-heat-shock-factor-1-hsf1-phosphorylation-deregulates-its-activity-and-lowers-activation-threshold-leading-to-obesity-in-mice
#2
Xiongjie Jin, Aijun Qiao, Demetrius Moskophidis, Nahid F Mivechi
Heat shock factor 1 (Hsf1) is transcriptionally activated following exposure of mammalian cells to environmental insults and pathological conditions. The function of Hsf1 as a protector of cells and organisms towards a range of stress stimuli has been well-documented. However, how different Hsf1 post-transcriptional modifications affect its function in vivo is not understood. Hsf1 transcriptional activity is in part regulated by phosphorylation. Hsf1 phosphorylation of amino acid residues at S303 and S307 has been shown to repress Hsf1 transcriptional activity under normal physiological growth conditions...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28710461/bromodomain-factors-of-bet-family-are-new-essential-actors-of-pericentric-heterochromatin-transcriptional-activation-in-response-to-heat-shock
#3
Edwige Col, Neda Hoghoughi, Solenne Dufour, Jessica Penin, Sivan Koskas, Virginie Faure, Maria Ouzounova, Hector Hernandez-Vargash, Nicolas Reynoird, Sylvain Daujat, Eric Folco, Marc Vigneron, Robert Schneider, André Verdel, Saadi Khochbin, Zdenko Herceg, Cécile Caron, Claire Vourc'h
The heat shock response is characterized by the transcriptional activation of both hsp genes and noncoding and repeated satellite III DNA sequences located at pericentric heterochromatin. Both events are under the control of Heat Shock Factor I (HSF1). Here we show that under heat shock, HSF1 recruits major cellular acetyltransferases, GCN5, TIP60 and p300 to pericentric heterochromatin leading to a targeted hyperacetylation of pericentric chromatin. Redistribution of histone acetylation toward pericentric region in turn directs the recruitment of Bromodomain and Extra-Terminal (BET) proteins BRD2, BRD3, BRD4, which are required for satellite III transcription by RNAP II...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28707656/-regulation-of-heat-shock-gene-expression-in-response-to-stress
#4
D G Garbuz
Heat shock (HS) genes, or stress genes, code for a number of proteins that collectively form the most ancient and universal stress defense system. The system determines the cell capability of adaptation to various adverse factors and performs a variety of auxiliary functions in normal physiological conditions. Common stress factors, such as higher temperatures, hypoxia, heavy metals, and others, suppress transcription and translation for the majority of genes, while HS genes are upregulated. Transcription of HS genes is controlled by transcription factors of the HS factor (HSF) family...
May 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28698764/modulatory-effect-of-monochromatic-blue-light-on-heat-stress-response-in-commercial-broilers
#5
Safaa E Abdo, Seham El-Kassas, Abeer F El-Nahas, Shawky Mahmoud
In a novel approach, monochromatic blue light was used to investigate its modulatory effect on heat stress biomarkers in two commercial broiler strains (Ross 308 and Cobb 500). At 21 days old, birds were divided into four groups including one group housed in white light, a second group exposed to blue light, a 3rd group exposed to white light + heat stress, and a 4th group exposed to blue light + heat stress. Heat treatment at 33°C lasted for five h for four successive days. Exposure to blue light during heat stress reduced MDA concentration and enhanced SOD and CAT enzyme activities as well as modulated their gene expression...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28686674/hsf1-and-hsf3-cooperatively-regulate-the-heat-shock-response-in-lizards
#6
Ryosuke Takii, Mitsuaki Fujimoto, Yuki Matsuura, Fangxu Wu, Namiko Oshibe, Eiichi Takaki, Arpit Katiyar, Hiroshi Akashi, Takashi Makino, Masakado Kawata, Akira Nakai
Cells cope with temperature elevations, which cause protein misfolding, by expressing heat shock proteins (HSPs). This adaptive response is called the heat shock response (HSR), and it is regulated mainly by heat shock transcription factor (HSF). Among the four HSF family members in vertebrates, HSF1 is a master regulator of HSP expression during proteotoxic stress including heat shock in mammals, whereas HSF3 is required for the HSR in birds. To examine whether only one of the HSF family members possesses the potential to induce the HSR in vertebrate animals, we isolated cDNA clones encoding lizard and frog HSF genes...
2017: PloS One
https://www.readbyqxmd.com/read/28680880/in-vitro-anticancer-effect-of-gedunin-on-human-teratocarcinomal-ntera-2-cancer-stem-like-cells
#7
Luxmiga Tharmarajah, Sameera Ranganath Samarakoon, Meran Keshawa Ediriweera, Poorna Piyathilaka, Kamani Hemamamla Tennekoon, Kanishka Sithira Senathilake, Umapriyatharshini Rajagopalan, Prasanna Bandula Galhena, Ira Thabrew
Gedunin is one of the major compounds found in the neem tree (Azadirachta indica). In the present study, antiproliferative potential of gedunin was evaluated in human embryonal carcinoma cells (NTERA-2, a cancer stem cell model) and peripheral blood mononuclear cells (PBMCs), using Sulforhodamine (SRB) and WST-1 assays, respectively. The effects of gedunin on expression of heat shock protein 90 (HSP90), its cochaperone Cdc37, and HSP client proteins (AKT, ErbB2, and HSF1) were evaluated by real-time PCR. Effects of gedunin on apoptosis were evaluated by (a) apoptosis associated morphological changes, (b) caspase 3/7 expression, (c) DNA fragmentation, (d) TUNEL assay, and (e) real-time PCR of apoptosis related genes (Bax, p53, and survivin)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28678786/bidirectional-interplay-of-hsf1-degradation-and-upr-activation-promotes-tau-hyperphosphorylation
#8
Eunhee Kim, Kazuko Sakata, Francesca-Fang Liao
The unfolded protein response (UPR) in the endoplasmic reticulum (ER) and the cytoplasmic heat stress response are two major stress response systems necessary for maintaining proteostasis for cellular health. Failure of either of these systems, such as in sustained UPR activation or in insufficient heat shock response activation, can lead to the development of neurodegeneration. Alleviation of ER stress and enhancement of heat shock response through heat shock factor 1 (HSF1) activation have previously been considered as attractive potential therapeutic targets for Alzheimer's disease (AD)-a prevalent and devastating tauopathy...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28638149/hsp90-inhibitor-induces-nuclear-translocation-of-hsf1-predominantly-in-hippocampal-ca1-region
#9
B Wang, Y Liu, L Huang, J Chen, J J Li, R Wang, E Kim, Y Chen, C Justicia, K Sakata, H Chen, A Planas, R S Ostrom, W Li, G Yang, M P McDonald, R Chen, D H Heck, F-F Liao
No abstract text is available yet for this article.
July 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28624953/genome-wide-analysis-of-differential-dna-methylation-in-silver-russell-syndrome
#10
Di Wu, Chunxiu Gong, Chang Su
Silver-Russell Syndrome (SRS) is clinically heterogeneous disorder characterized by low birth weight, postnatal growth restriction, and variable dysmorphic features. Current evidence strongly implicates imprinted genes as an important etiology of SRS. Although almost half of the patients showed DNA hypomethylation at the H19/IGF2 imprinted domain, and approximately 7%-10% of SRS patients have maternal uniparental disomy of chromosome 7 (UPD (7) mat); the rest of the SRS patients shows unknown etiology. In this study, we investigate whether there are further DNA methylation defects in SRS patients...
June 14, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28618124/pir-823-contributes-to-colorectal-tumorigenesis-by-enhancing-the-transcriptional-activity-of-hsf1
#11
Jie Yin, Xiao-Yu Jiang, Wei Qi, Chen-Guang Ji, Xiao-Li Xie, Dong-Xuan Zhang, Zi-Jin Cui, Cun-Kai Wang, Yun Bai, Jia Wang, Hui-Qing Jiang
Piwi-interacting RNAs (piRNAs), a novel class of small non-coding RNA, were first discovered in germline cells and are thought to silence transposons in spermatogenesis. Recently, piRNAs have also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. However, the function of piR-823 in colorectal cancer (CRC) remains unclear. Here, we first found that piR-823 was significantly up-regulated in CRC tissues compared with its expression in the adjacent tissues...
June 15, 2017: Cancer Science
https://www.readbyqxmd.com/read/28617974/high-expression-of-heat-shock-proteins-and-heat-shock-factor-1-distinguishes-an-aggressive-subset-of-clear-cell-renal-cell-carcinoma
#12
Pao-Shu Wu, Yen-Hwa Chang, Chin-Chen Pan
AIMS: Heat shock proteins (HSPs) are a group of molecules induced by a variety of environmental and pathophysiologic stresses, including cancer. HSPs are implicated in the regulation of apoptosis and immunity in neoplasm. Transcription factor heat shock factor1 (HSF1) acts as the master regulator to control HSP expression, and therefore is involved in tumorigenesis. The purpose of this study was to evaluate the expression and clinicopathologic relevance of HSPs and HSF1 in clear cell renal cell carcinoma (ccRCC)...
June 15, 2017: Histopathology
https://www.readbyqxmd.com/read/28598816/combined-inhibition-of-akt-and-hsf1-suppresses-breast-cancer-stem-cells-and-tumor-growth
#13
Richard L Carpenter, Sherona Sirkisoon, Dongqin Zhu, Tadas Rimkus, Alexandria Harrison, Ashley Anderson, Ivy Paw, Shadi Qasem, Fei Xing, Yin Liu, Michael Chan, Linda Metheny-Barlow, Boris C Pasche, Waldemar Debinski, Kounosuke Watabe, Hui-Wen Lo
Breast cancer is the most common cancer in women and the second leading cause of cancer deaths in women. Over 90% of breast cancer deaths are attributable to metastasis. Our lab has recently reported that AKT activates heat shock factor 1 (HSF1), leading to epithelial-to-mesenchymal transition in HER2-positive breast cancer. However, it is unknown whether the AKT-HSF1 pathway plays an important role in other breast cancer subtypes, breast cancer stem cells, or breast cancer growth and metastasis. Herein, we showed AKT and HSF1 to be frequently co-activated in breast cancer cell lines and specimens across different subtypes...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28592492/heterogeneous-nuclear-ribonucleoprotein-k-inhibits-heat-shock-induced-transcriptional-activity-of-heat-shock-factor-1
#14
Hee-Jung Kim, Jae-Jin Lee, Jin-Hwan Cho, Jaeho Jeong, A Young Park, Wonmo Kang, Kong-Joo Lee
When cells are exposed to heat shock and various other stresses, heat shock factor 1 (HSF1) is activated and the heat shock response (HSR) is elicited. To better understand the molecular regulation of the HSR, we used 2D-PAGE based proteome analysis to screen for heat shock-induced posttranslationally modified cellular proteins. Our analysis revealed that two protein spots typically present on 2D-PAGE gels and containing heterogeneous nuclear ribonucleoprotein K (hnRNP K) with trioxidized Cys132 disappeared after the heat shock treatment and reappeared during recovery, but the total amount of hnRNP K protein remained unchanged...
June 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28586010/resveratrol-protects-against-l-arginine-induced-acute-necrotizing-pancreatitis-in-mice-by-enhancing-sirt1-mediated-deacetylation-of-p53-and-heat-shock-factor-1
#15
Nian Wang, Fen Zhang, Liu Yang, Jiang Zou, Hao Wang, Ke Liu, Meidong Liu, Huali Zhang, Xianzhong Xiao, Kangkai Wang
Acute necrotizing pancreatitis (ANP) is a common severe critical illness with a high mortality rate. Resveratrol, a polyphenol compound derived from various plants such as grape skin, peanut, berry and veratrum, exhibits multiple biological activities, especially potent anti‑inflammatory activity, but its effect on ANP has not yet been fully elucidated. The present study aimed to investigate the effects of resveratrol on L-arginine-induced ANP and the possible mechanisms. A mouse model of ANP was established by 2 hourly intraperitoneal injections of 8% L-arginine (4 g/kg)...
June 6, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28575284/role-of-heat-shock-factor-1-in-conserving-cholesterol-transportation-in-leydig-cell-steroidogenesis-via-steroidogenic-acute-regulatory-protein
#16
Shintaro Oka, Koji Shiraishi, Mitsuaki Fujimoto, Arpit Katiyar, Ryosuke Takii, Akira Nakai, Hideyasu Matsuyama
Testicular testosterone synthesis begins with cholesterol transport into mitochondria via steroidogenic acute regulatory protein (StAR) in Leydig cells. Acute heat stress is known to obstruct testicular steroidogenesis by transcriptional repression of StAR. In contrast, chronic heat stress such as cryptorchidism or varicocele generally does not affect testicular steroidogenesis, suggesting that Leydig cells adapt to heat stress and retain their steroid synthesis ability. However, the mechanisms of the stress response in steroid-producing cells are unclear...
May 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/28560416/xaf1-expression-levels-in-a-non-small-cell-lung-cancer-cohort-and-its-potential-association-with-carcinogenesis
#17
Luciene Schluckebier, Veronica Aran, Joyce De Moraes, Heitor Paiva, Cinthya Sternberg, Carlos Gil Ferreira
The process of lung carcinogenesis is still not well understood and involves different levels of regulation of several genes. The search for molecular biomarkers, which can be applicable to clinical practice, has been the focus of various studies. XIAP-associated factor 1 (XAF1) was previously shown to be downregulated in many types of tumors, including squamous cell lung cancer. XAF1 is a pro-apoptotic protein and its restoration was found to sensitize cancer cells to apoptotic stimuli; however, the precise mechanism involved in the downregulation of XAF1 in tumors is unknown and promoter hypermethylation or heat-shock transcription factor 1 (HSF1) may be involved...
May 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28557624/rna-guided-activation-of-pluripotency-genes-in-human-fibroblasts
#18
Kai Xiong, Yan Zhou, Kristian Aabo Blichfeld, Poul Hyttel, Lars Bolund, Kristine Karla Freude, Yonglun Luo
Specific activation of endogenous genes can be achieved by programmable artificial transcription factors (ATFs). In this study, we compared two artificial, programmable, clustered regularly interspaced short palindromic repeats (CRISPR)-based, ubiquitous transcription factors: deficient CRISPR-associated protein 9 (dCas9)-VP64 (CRISPRa) alone, or a combination of dCas9-VP64 and MS2-P65-HSF1 [synergistic activation mediator (SAM) system] mediated activation of five pluripotency genes: KLF4 (K), LIN28 (L), MYC (M), OCT4 (O), and SOX2 (S) in human cells (HEK293T, HeLa, HepG2, and primary fibroblasts)...
June 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28547133/hsf1-acetylation-decreases-its-transcriptional-activity-and-enhances-glucolipotoxicity-induced-apoptosis-in-rat-and-human-beta-cells
#19
Indri Purwana, Jun J Liu, Bernard Portha, Jean Buteau
AIMS/HYPOTHESIS: Heat shock factor protein 1 (HSF1) is a transcription factor that regulates the expression of key molecular chaperones, thereby orchestrating the cellular response to stress. This system was recently implicated in the control of insulin sensitivity and is therefore being scrutinised as a novel therapeutic avenue for type 2 diabetes. However, the regulation and biological actions of HSF1 in beta cells remain elusive. Herein, we sought to investigate the regulation of HSF1 in pancreatic beta cells and to study its potential role in cell survival...
May 25, 2017: Diabetologia
https://www.readbyqxmd.com/read/28542269/the-small-molecule-kinase-inhibitor-d11-counteracts-17-aag-mediated-up-regulation-of-hsp70-in-brain-cancer-cells
#20
Susanne Schaefer, Tina H Svenstrup, Barbara Guerra
Many types of cancer express high levels of heat shock proteins (HSPs) that are molecular chaperones regulating protein folding and stability ensuring protection of cells from potentially lethal stress. HSPs in cancer cells promote survival, growth and spreading even in situations of growth factors deprivation by associating with oncogenic proteins responsible for cell transformation. Hence, it is not surprising that the identification of potent inhibitors of HSPs, notably HSP90, has been the primary research focus, in recent years...
2017: PloS One
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