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https://www.readbyqxmd.com/read/27909049/control-of-secreted-protein-gene-expression-and-the-mammalian-secretome-by-the-metabolic-regulator-pgc-1%C3%AE
#1
Neri Minsky, Robert G Roeder
Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. However, how the secretome is regulated remains incompletely understood. Here we demonstrate, unexpectedly, that peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate expression of diverse genes encoding secreted molecules and extracellular matrix (ECM) components to modulate the secretome...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27906968/structural-and-functional-recovery-of-sensory-cilia-in-c-elegans-ift-mutants-upon-aging
#2
Astrid Cornils, Ashish K Maurya, Lauren Tereshko, Julie Kennedy, Andrea G Brear, Veena Prahlad, Oliver E Blacque, Piali Sengupta
The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27890044/effect-of-dietary-manganese-on-antioxidant-status-and-expressions-of-heat-shock-proteins-and-factors-in-tissues-of-laying-broiler-breeders-under-normal-and-high-environmental-temperatures
#3
Yong-Wen Zhu, Lin Lu, Wen-Xiang Li, Li-Yang Zhang, Cheng Ji, Xi Lin, Hsiao-Ching Liu, Jack Odle, Xu-Gang Luo
To investigate the effect of Mn on antioxidant status and on the expressions of heat shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21±1°C, and high, 32±1°C)×3 dietary Mn treatments (a Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet, either as inorganic Mn sulphate (iMn) or as organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in any of the measured indices...
November 28, 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/27889440/non-heat-shock-responsive-roles-of-hsf1-in-candida-albicans-are-essential-under-iron-deprivation-and-drug-defense
#4
Remya Nair, Mohd Shariq, Sanjiveeni Dhamgaye, Chinmay K Mukhopadhyay, Shamim Shaikh, Rajendra Prasad
Recently, we have reported that the conditional mutant of the heat shock factor-1 (HSF1) in Candida albicans displays enhanced susceptibility not only towards a plant alkaloid, berberine, but also to diverse antifungal drugs. The present study attempts to identify additional phenotypes highlighting the non-heat shock responsive roles of HSF1 that could be correlated with the enhanced drug susceptibility. We uncover an intricate relationship between cellular iron and HSF1 mediated drug susceptibility of C. albicans...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27888001/antioxidants-and-hne-in-redox-homeostasis
#5
REVIEW
Wojciech Łuczaj, Agnieszka Gęgotek, Elżbieta Skrzydlewska
Under physiological conditions, cells are in a stable state known as redox homeostasis, which is maintained by the balance between continuous ROS/RNS generation and several mechanisms involved in antioxidant activity. ROS overproduction results in alterations in the redox homeostasis that promote oxidative damage to major components of the cell, including the biomembrane phospholipids. Lipid peroxidation subsequently generates a diverse set of products, including α,β-unsaturated aldehydes. Of these products, 4-hydroxy-2-nonenal (HNE) is the most studied aldehyde on the basis of its involvement in cellular physiology and pathology...
November 22, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27866167/rewiring-of-signaling-networks-modulating-thermotolerance-in-the-human-pathogen-cryptococcus-neoformans
#6
Dong-Hoon Yang, Kwang-Woo Jung, Soohyun Bang, Jang-Won Lee, Min-Hee Song, Anna Floyd-Averette, Richard A Festa, Giuseppe Ianiri, Alexander Idnurm, Dennis J Thiele, Joseph Heitman, Yong-Sun Bahn
Thermotolerance is a crucial virulence attribute for human pathogens, including the fungus Cryptococcus neoformans that causes fatal meningitis in humans. Loss of the protein kinase Sch9 increases C. neoformans thermotolerance, but its regulatory mechanism has remained unknown. Here, we studied the Sch9-dependent and Sch9-independent signaling networks modulating C. neoformans thermotolerance by using genome-wide transcriptome analysis and reverse genetic approaches. During temperature upshift, genes encoding for molecular chaperones and heat shock proteins were upregulated, whereas those for translation, transcription, and sterol biosynthesis were highly suppressed...
November 18, 2016: Genetics
https://www.readbyqxmd.com/read/27846716/-mechanisms-of-protein-homeostasis-regulation-in-cancer-development
#7
F Trčka, P Müller, B Vojtěšek
BACKGROUND: The proteome of eukaryotic cells represents a complex system. Its components are exposed to various intrinsic and extrinsic stresses. Therefore, the function of the cellular proteome is dependent on the existence of compensatory mechanisms balancing the inner protein homeostasis - proteostasis. These mechanisms involve the network of molecular chaperones and transcriptional program regulating their expression. The process of cancerogenesis is accompanied by significant changes in the intracellular milieu of cancer cells - temperature, pH, availability of nutrients...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27846364/hsf1-stress-response-pathway-regulates-autophagy-receptor-sqstm1-p62-associated-proteostasis
#8
Yoshihisa Watanabe, Atsushi Tsujimura, Katsutoshi Taguchi, Masaki Tanaka
Proteostasis is important for protecting cells from harmful proteins and is mainly controlled by the HSF1 (heat shock transcription factor 1) stress response pathway. This pathway facilitates protein refolding by molecular chaperones; however, it is unclear whether it functions in autophagy or inclusion formation. The autophagy receptor SQSTM1/p62 is involved in selective autophagic clearance and inclusion formation by harmful proteins, and its phosphorylation at S349, S403, and S407 is required for binding to substrates...
November 15, 2016: Autophagy
https://www.readbyqxmd.com/read/27835876/azadiradione-ameliorates-polyglutamine-expansion-disease-in-drosophila-by-potentiating-dna-binding-activity-of-heat-shock-factor-1
#9
Vinod K Nelson, Asif Ali, Naibedya Dutta, Suvranil Ghosh, Manas Jana, Arnab Ganguli, Andrei Komarov, Soumyadip Paul, Vibha Dwivedi, Subhrangsu Chatterjee, Nihar R Jana, Subhash C Lakhotia, Gopal Chakrabarti, Anup K Misra, Subhash C Mandal, Mahadeb Pal
Aggregation of proteins with the expansion of polyglutamine tracts in the brain underlies progressive genetic neurodegenerative diseases (NDs) like Huntington's disease and spinocerebellar ataxias (SCA). An insensitive cellular proteotoxic stress response to non-native protein oligomers is common in such conditions. Indeed, upregulation of heat shock factor 1 (HSF1) function and its target protein chaperone expression has shown promising results in animal models of NDs. Using an HSF1 sensitive cell based reporter screening, we have isolated azadiradione (AZD) from the methanolic extract of seeds of Azadirachta indica, a plant known for its multifarious medicinal properties...
October 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27831650/critical-genes-of-hepatocellular-carcinoma-revealed-by-network-and-module-analysis-of-rna-seq-data
#10
M-R Yang, Y Zhang, X-X Wu, W Chen
OBJECTIVE: RNA-seq data of hepatocellular carcinoma (HCC) was analyzed to identify critical genes related to the pathogenesis and prognosis. MATERIALS AND METHODS: Three RNA-seq datasets of HCC (GSE69164, GSE63863 and GSE55758) were downloaded from Gene Expression Omnibus (GEO), while another dataset including 54 HCC cases with survival time was obtained from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) were identified by significant analysis of microarrays (SAM) method using package samr of R...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27831465/dynamic-control-of-hsf1-during-heat-shock-by-a-chaperone-switch-and-phosphorylation
#11
Xu Zheng, Joanna Krakowiak, Nikit Patel, Ali Beyzavi, Jideofor Ezike, Ahmad S Khalil, David Pincus
Heat shock factor (Hsf1) regulates the expression of molecular chaperones to maintain protein homeostasis. Despite its central role in stress resistance, disease and aging, the mechanisms that control Hsf1 activity remain unresolved. Here we show that in budding yeast, Hsf1 basally associates with the chaperone Hsp70 and this association is transiently disrupted by heat shock, providing the first evidence that a chaperone repressor directly regulates Hsf1 activity. We develop and experimentally validate a mathematical model of Hsf1 activation by heat shock in which unfolded proteins compete with Hsf1 for binding to Hsp70...
November 10, 2016: ELife
https://www.readbyqxmd.com/read/27812889/use-of-conditioned-media-is-critical-for-studies-of-regulation-in-response-to-rapid-heat-shock
#12
Dig B Mahat, John T Lis
Heat shock response (HSR) maintains and restores protein homeostasis when cells are exposed to proteotoxic heat stress. Heat shock (HS) triggers a rapid and robust change in genome-wide transcription, protein synthesis, and chaperone activity; and therefore, the HSR has been widely used as a model system in these studies. The conventional method of performing instantaneous HS in the laboratory uses heated fresh media to induce HSR when added to cells. However, addition of fresh media to cells may evoke additional cellular responses and signaling pathways...
November 3, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27809308/doxorubicin-attenuates-chip-guarded-hsf1-nuclear-translocation-and-protein-stability-to-trigger-igf-iir-dependent-cardiomyocyte-death
#13
Chih-Yang Huang, Wei-Wen Kuo, Jeng-Fan Lo, Tsung-Jung Ho, Pei-Ying Pai, Shu-Fen Chiang, Pei-Yu Chen, Fu-Jen Tsai, Chang-Hai Tsai, Chih-Yang Huang
Doxorubicin (DOX) is one of the most effective antitumor drugs, but its cardiotoxicity has been a major concern for its use in cancer therapy for decades. Although DOX-induced cardiotoxicity has been investigated, the underlying mechanisms responsible for this cardiotoxicity have not been completely elucidated. Here, we found that the insulin-like growth factor receptor II (IGF-IIR) apoptotic signaling pathway was responsible for DOX-induced cardiotoxicity via proteasome-mediated heat shock transcription factor 1 (HSF1) degradation...
November 3, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27803431/m3-muscarinic-receptor-signaling-stabilizes-a-novel-mutant-human-ether-a-go-go-related-gene-channel-protein-via-phosphorylation-of-heat-shock-factor-1-in-transfected-cells
#14
Endang Mahati, Peili Li, Yasutaka Kurata, Nani Maharani, Nobuhito Ikeda, Shinji Sakata, Kazuyoshi Ogura, Junichiro Miake, Takeshi Aiba, Wataru Shimizu, Naoe Nakasone, Haruaki Ninomiya, Katsumi Higaki, Kazuhiro Yamamoto, Akira Nakai, Yasuaki Shirayoshi, Ichiro Hisatome
BACKGROUND: Long QT syndrome 2 (LQT2) is caused by mutations in the human ether-a-go-go-related gene (hERG). Most of its mutations give rise to unstable hERG proteins degraded by the proteasome. Recently, carbachol was reported to stabilize the wild-type hERG-FLAG via activation of the muscarinic type 3 receptor (M3-mAChR). Its action on mutant hERG-FLAG, however, remains uninvestigated.Methods and Results:A novel mutant hERG-FLAG carried 2 mutations: an amino acid substitution G572S and an in-frame insertion D1037_V1038insGD...
November 1, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27799305/heat-shock-protein-90-facilitates-latent-hiv-reactivation-through-maintaining-the-function-of-positive-transcriptional-elongation-factor-b-p-tefb-under-proteasome-inhibition
#15
Xiao-Yan Pan, Wei Zhao, Chun-Yan Wang, Jian Lin, Xiao-Yun Zeng, Ru-Xia Ren, Keng Wang, Tian-Rong Xun, Yechiel Shai, Shu-Wen Liu
The persistence of HIV in resting memory CD4+ T cells at a latent state is considered as the major barrier on the path to achieve a cure for HIV. Proteasome inhibitors (PIs) were previously reported as latency reversing agents (LRAs) but the mechanism underlying this function is yet unclear. Here we demonstrate that PIs reactivate latent HIV ex vivo without global T cell activation, and may facilitate host innate immune responses. Mechanistically, latent HIV reactivation induced by PIs is mediated by heat shock factor 1 (HSF1) via the recruitment of the heat shock protein (HSP) 90-positive transcriptional elongation factor b (p-TEFb) complex...
October 31, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27796344/antileukemic-scalarane-sesterterpenoids-and-meroditerpenoid-from-carteriospongia-phyllospongia-sp-induce-apoptosis-via-dual-inhibitory-effects-on-topoisomerase-ii-and-hsp90
#16
Kuei-Hung Lai, Yi-Chang Liu, Jui-Hsin Su, Mohamed El-Shazly, Chih-Fung Wu, Ying-Chi Du, Yu-Ming Hsu, Juan-Cheng Yang, Ming-Kai Weng, Chia-Hua Chou, Guan-Yu Chen, Yu-Cheng Chen, Mei-Chin Lu
Two new scalarane sesterterpenoids, 12β-(3'β-hydroxybutanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (1) and 12β-(3'β-hydroxypentanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (2), along with one known tetraprenyltoluquinol-related metabolite (3), were isolated from the sponge Carteriospongia sp. In leukemia Molt 4 cells, 1 at 0.0625 μg/mL (125 nM) triggered mitochondrial membrane potential (MMP) disruption and apoptosis showing more potent effect than 2 and 3. The isolates inhibited topoisomerase IIα expression...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27791982/erbb2-inhibition-by-lapatinib-promotes-degradation-of-mutant-p53-protein-in-cancer-cells
#17
Dun Li, Natalia D Marchenko
Mutations in the p53 tumor suppressor gene are the most prevalent genetic events in human Her2-positive breast cancer and are associated with poor prognosis and survival. Human clinical data and our in vitro and in vivo studies strongly suggest potent oncogenic cooperation between mutant p53 and Her2 (ErbB2). Yet, the translational significance of mutant p53 in Her2 positive breast cancer, especially with respect to Her2-targeted therapies, has not been evaluated. Our previous work identified novel oncogenic activity of mutant p53 whereby mutp53 amplifies ErbB2 signaling via the mutp53-HSF1-ErbB2 feed-forward loop...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27787597/stromal-factors-involved-in-human-prostate-cancer-development-progression-and-castration-resistance
#18
Noemi Eiro, Jesus Fernandez-Gomez, Raquel Sacristán, Belen Fernandez-Garcia, Beatriz Lobo, Jorge Gonzalez-Suarez, Alejandro Quintas, Safwan Escaf, Francisco J Vizoso
PURPOSE: To detect new predictive markers from the prostate cancer tissue, to study the expression by cultured cancer-associated fibroblasts (CAFs) of stromal factors implicated in prostate carcinogenesis, and to compare their expressions in localized, metastatic, castration-sensitive (CSCP), castration-resistant prostate tumors (CRCP) as well as in fibroblasts from benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: The genomic expression of 20 stroma-derived factors, including the androgen receptor (AR), growth factors (FGF2, FGF7, FGF10, HGF, TGFβ, PDGFB), protein implicated in invasion (MMP-2, MMP-9 and MMP-11), inflammation (IL-6, IL-17, STAT-3 and NFκB), stroma/epithelium interaction (CDH11, FAP, CXCL12 and CXCL14) and chaperones (HPA1A and HSF1), was evaluated in cultured fibroblasts both from BHP and prostate carcinomas (PCa)...
October 27, 2016: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27777286/interference-with-the-hsf1-hsp70-bag3-pathway-primes-glioma-cells-to-matrix-detachment-and-bh3-mimetic-induced-apoptosis
#19
Patrick Antonietti, Benedikt Linder, Stephanie Hehlgans, Iris C Mildenberger, Michael C Burger, Simone Fulda, Joachim P Steinbach, Florian Gessler, Franz Rodel, Michel Mittelbronn, Donat Kogel
Malignant gliomas exhibit a high intrinsic resistance against stimuli triggering apoptotic cell death. HSF1 (heat shock factor 1) acts as transcription factor upstream of HSP70 and the HSP70 co-chaperone BAG3 that is overexpressed in glioblastoma. To specifically target this resistance mechanism, we applied the selective HSF1 inhibitor KRIBB11 and the HSP70/BAG3 interaction inhibitor YM-1 in combination with the pan-Bcl-2 inhibitor AT-101. Here we demonstrate that lentiviral BAG3 silencing significantly enhances AT-101-induced cell death and reactivates effector caspase-mediated apoptosis in U251 glioma cells with high BAG3 expression, while these sensitizing effects were less pronounced in U343 cells expressing lower BAG3 levels...
October 24, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27773730/molecular-cloning-of-orange-spotted-grouper-epinephelus-coioides-heat-shock-transcription-factor-1-isoforms-and-characterization-of-their-expressions-in-response-to-nodavirus
#20
Ting-Yu Wang, Young-Mao Chen, Tzong-Yueh Chen
Heat shock transcription factor 1 (HSF1) regulates heat shock proteins (HSPs), which assist in protein folding and inhibit protein denaturation following stress. HSF1 was firstly cloned from orange-spotted grouper and exists as two isoforms, one with (osgHSF1a) and one without (osgHSF1b) exon 11. Heat exposure increased the expression of osgHSF1b while cold exposure increased that of osgHSF1a. Both isoforms were mainly expressed in the brains, eyes, and fins. Expression of osgHSF1b was higher than osgHSF1a during development...
December 2016: Fish & Shellfish Immunology
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