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https://www.readbyqxmd.com/read/29769566/antiretroviral-drugs-alter-the-content-of-extracellular-vesicles-from-hiv-1-infected-cells
#1
Catherine DeMarino, Michelle L Pleet, Maria Cowen, Robert A Barclay, Yao Akpamagbo, James Erickson, Nicaise Ndembe, Manhattan Charurat, Jibreel Jumare, Sunday Bwala, Peter Alabi, Max Hogan, Archana Gupta, Nicole Noren Hooten, Michele K Evans, Benjamin Lepene, Weidong Zhou, Massimo Caputi, Fabio Romerio, Walter Royal, Nazira El-Hage, Lance A Liotta, Fatah Kashanchi
To date, the most effective treatment of HIV-1 is a combination antiretroviral therapy (cART), which reduces viral replication and reverses pathology. We investigated the effect of cART (RT and protease inhibitors) on the content of extracellular vesicles (EVs) released from HIV-1-infected cells. We have previously shown that EVs contain non-coding HIV-1 RNA, which can elicit responses in recipient cells. In this manuscript, we show that TAR RNA levels demonstrate little change with the addition of cART treatment in cell lines, primary macrophages, and patient biofluids...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29766042/bc-rna-mislocalization-in-the-fragile-x-premutation
#2
Ilham A Muslimov, Taesun Eom, Anna Iacoangeli, Shih-Chieh Chuang, Renate K Hukema, Rob Willemsen, Dimitre G Stefanov, Robert K S Wong, Henri Tiedge
Fragile X premutation disorder is caused by CGG triplet repeat expansions in the 5' untranslated region of FMR1 mRNA. The question of how expanded CGG repeats cause disease is a subject of continuing debate. Our work indicates that CGG-repeat structures compete with regulatory BC1 RNA for access to RNA transport factor hnRNP A2. As a result, BC1 RNA is mislocalized in vivo, as its synapto-dendritic presence is severely diminished in brains of CGG-repeat knock-in animals (a premutation mouse model). Lack of BC1 RNA is known to cause seizure activity and cognitive dysfunction...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29762696/blocking-of-an-intronic-splicing-silencer-completely-rescues-ikbkap-exon-20-splicing-in-familial-dysautonomia-patient-cells
#3
Gitte H Bruun, Jeanne Mv Bang, Lise L Christensen, Sabrina Brøner, Ulrika Ss Petersen, Barbara Guerra, Alexander Gb Grønning, Thomas K Doktor, Brage S Andresen
Familial dysautonomia (FD) is a severe genetic disorder causing sensory and autonomic dysfunction. It is predominantly caused by a c.2204+6T>C mutation in the IKBKAP gene. This mutation decreases the 5' splice site strength of IKBKAP exon 20 leading to exon 20 skipping and decreased amounts of full-length IKAP protein. We identified a binding site for the splicing regulatory protein hnRNP A1 downstream of the IKBKAP exon 20 5'-splice site. We show that hnRNP A1 binds to this splicing regulatory element (SRE) and that two previously described inhibitory SREs inside IKBKAP exon 20 are also bound by hnRNP A1...
May 14, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29724888/hnrnp-k-plays-a-protective-role-in-tnf-%C3%AE-induced-apoptosis-in-podocytes
#4
Shili Zhao, Junxia Feng, Qi Wang, Lu Tian, Yunfang Zhang, Hongyan Li
Apoptosis of podocytes contributes to proteinuria in many chronic kidney diseases. The cytokine, tumor necrosis factor-alpha (TNF-α) is thought to be involved in podocyte apoptosis, but the underlying mechanism is not understood. In our study, we established a model of TNF-α-induced apoptosis by isolating primary podocytes from mice. After exposing cells to TNF-α, we determined the expression levels of hnRNP K and c-FLIP and the phosphorylation levels of GSK3β and ERK. We then knocked down or overexpressed the levels of hnRNP K and observed its effects on the expressions of c-FLIP, caspase-8, caspase-3, and the phosphorylation of GSK3β and ERK...
May 3, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29695777/a-sumo-dependent-feedback-loop-senses-and-controls-the-biogenesis-of-nuclear-pore-subunits
#5
Jérôme O Rouvière, Manuel Bulfoni, Alex Tuck, Bertrand Cosson, Frédéric Devaux, Benoit Palancade
While the activity of multiprotein complexes is crucial for cellular metabolism, little is known about the mechanisms that collectively control the expression of their components. Here, we investigate the regulations targeting the biogenesis of the nuclear pore complex (NPC), the macromolecular assembly mediating nucleocytoplasmic exchanges. Systematic analysis of RNA-binding proteins interactomes, together with in vivo and in vitro assays, reveal that a subset of NPC mRNAs are specifically bound by Hek2, a yeast hnRNP K-like protein...
April 25, 2018: Nature Communications
https://www.readbyqxmd.com/read/29693745/human-apobec3b-interacts-with-the-heterogenous-nuclear-ribonucleoprotein-a3-in-cancer-cells
#6
Nawneet Mishra, K Sony Reddy, Uddhav Timilsina, Deepak Gaur, Ritu Gaur
Human APOBEC3B (A3B), like other APOBEC3 members, is a cytosine deaminase which causes hypermutation of single stranded genome. Recent studies have shown that A3B is predominantly elevated in multiple cancer tissues and cell lines such as the bladder, cervix, lung, head and neck, and breast. Upregulation and activation of A3B in developing tumors can cause an unexpected cluster of mutations which promote cancer development and progression. The cellular proteins which facilitate A3B function through direct or indirect interactions remain largely unknown...
April 25, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29480994/impact-of-cyclin-d1-and-heterogeneous-nuclear-ribonucleoprotein-k-hnrnp-k-on-urinary-bladder-carcinogenesis
#7
Tarek Aboushousha, Olfat Hammam, Noha Helal, Samir El Dahshan
Objective: This study aimed to investigate the expression of cyclin D1 and hnRNP-K in relation to the pathological findings in bladder cancer including the type, grade, muscle invasion and bilharzial association. Methods: We studied the immunoexpression; as regard the percentage, intensity and score of both cyclin D1 and hnRNP-K in different bladder lesions including 10 cases of cystitis; 10 cases of carcinoma insitu (CIS), 20 cases of Squamous cell carcinoma (SCC) and 66 cases of urothelial carcinoma (UC)...
February 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29409808/long-non-coding-rna-linc00460-promotes-epithelial-mesenchymal-transition-and-cell-migration-in-lung-cancer-cells
#8
Ke Li, Dan Sun, Qiheng Gou, Xixian Ke, Yanqiu Gong, Yuanli Zuo, Jian-Kang Zhou, Chenglin Guo, Zhichu Xia, Lunxu Liu, Qintong Li, Lunzhi Dai, Yong Peng
Long non-coding RNAs (lncRNAs) function as critical regulators to participate in tumor progression and metastasis. However, their roles in non-small cell lung cancer (NSCLC) are poorly understood. In this study, we found that the expression of the lncRNA linc00460 is significantly upregulated in NSCLC tumors and associated with poor prognosis for NSCLC patients, implying that linc00460 is important for lung cancer development. The accurate transcription initiation and termination sites of linc00460 were then identified by rapid-amplification of cDNA ends (RACE) technologies, and the sequencing data demonstrated that linc00460, predominantly located in the cytoplasm of lung cancer cells, is a novel transcript variant...
April 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29321325/the-identification-and-characterization-of-sindbis-virus-rna-host-protein-interactions
#9
Autumn T LaPointe, Natasha N Gebhart, Megan E Meller, Richard W Hardy, Kevin J Sokoloski
Arthropod-borne viruses, such as the members of genus Alphavirus , are a significant concern to global public health. As obligate intracellular pathogens, RNA viruses must interact with the host cell machinery to establish, and complete, their viral lifecycles. Despite considerable efforts to define the host/pathogen interactions essential for alphaviral replication, an unbiased and inclusive assessment of alphaviral RNA:protein interactions has not been undertaken. Moreover, the biological and molecular importance of these interactions, in the full context of their molecular function as RNA-binding proteins, has not been fully realized...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29296177/isg15-silencing-increases-cisplatin-resistance-via-activating-p53-mediated-cell-dna-repair
#10
Yi Huo, Zhaoyun Zong, Qingtao Wang, Zhenyu Zhang, Haiteng Deng
Tumor cells frequently evolved resistance to cisplatin that greatly compromises the efficacy of chemotherapy. Identification of the mechanisms underlying drug resistance is important for developing new therapeutic approaches. ISG15 is found to be elevated in many human carcinomas and cancer cell lines. Here, we identified that the expressions of ISG15 and ISG15-conjugating system were downregulated in drug resistant A549/DDP cells compared to drug sensitive A549 cells. Silencing of ISG15 robustly elevated the resistance to cisplatin, suggesting ISG15 plays an important role in cisplatin resistance...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29213352/echinacoside-alleviates-uvb-irradiation-mediated-skin-damage-via-inhibition-of-oxidative-stress-dna-damage-and-apoptosis
#11
Di Zhang, Chengtao Lu, Zhe Yu, Xiayin Wang, Li Yan, Juanli Zhang, Hua Li, Jianbo Wang, Aidong Wen
Ultraviolet B (UVB) irradiation has been known to cause skin damage, which is associated with oxidative stress, DNA damage, and apoptosis. Echinacoside is a phenylethanoid glycoside isolated from Herba Cistanches , which exhibits strong antioxidant activity. In this study, we evaluate the photoprotective effect of echinacoside on UVB-induced skin damage and explore the potential molecular mechanism. BALB/c mice and HaCaT cells were treated with echinacoside before UVB exposure. Histopathological examination was used to evaluate the skin damage...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29191962/nontypeable-haemophilus-influenzae-lysates-increase-heterogeneous-nuclear-ribonucleoprotein-secretion-and-exosome-release-in-human-middle-ear-epithelial-cells
#12
Stéphanie Val, Anna Krueger, Marian Poley, Ariella Cohen, Kristy Brown, Aswini Panigrahi, Diego Preciado
Nontypeable Haemophilus influenzae (NTHi), one of the most common acute otitis media (OM) pathogens, is postulated to promote middle-ear epithelial remodeling in the progression of OM from acute to chronic. The goal of this study was to examine early quantitative proteomic secretome effects of NTHi lysate exposure in a human middle-ear epithelial cell (HMEEC) line. NTHi lysates were used to stimulate HMEEC, and conditional quantitative stable isotope labeling with amino acids in cell culture of cell secretions was performed...
January 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28982131/mex3c-interacts-with-adaptor-related-protein-complex-2-and-involves-in-mir-451a-exosomal-sorting
#13
Pin Lu, Huanhuan Li, Ning Li, Ravi N Singh, Colin E Bishop, Xiangxian Chen, Baisong Lu
Some RNA species, especially microRNAs, are non-randomly sorted into exosomes, but how selectivity of RNA exosomal sorting is achieved is unknown. We found that all three variants of RNA-binding ubiquitin E3 ligase (MEX3C)-MEX3C-1, MEX3C-2, and MEX3C-3 -interact with adaptor-related protein complex 2 (AP-2), a cargo adaptor in clathrin-mediated endocytosis. MEX3C's C-terminal RING finger domain and the hnRNP K homology (KH) domain shared by the three MEX3C variants are both necessary for MEX3C/AP-2 interaction...
2017: PloS One
https://www.readbyqxmd.com/read/28975734/a-jack-of-all-trades-the-rna-binding-protein-vigilin
#14
REVIEW
Matthew Hk Cheng, Ralf-Peter Jansen
The vigilin family of proteins is evolutionarily conserved from yeast to humans and characterized by the proteins' 14 or 15 hnRNP K homology (KH) domains, typically associated with RNA-binding. Vigilin is the largest RNA-binding protein (RBP) in the KH domain-containing family and one of the largest RBP known to date. Since its identification 30 years ago, vigilin has been shown to bind over 700 mRNAs and has been associated with cancer progression and cardiovascular disease. We provide a brief historic overview of vigilin research and outline the proteins' different functions, focusing on maintenance of genome ploidy, heterochromatin formation, RNA export, as well as regulation of translation, mRNA transport, and mRNA stability...
November 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28825698/a-regulated-pnuts-mrna-to-lncrna-splice-switch-mediates-emt-and-tumour-progression
#15
Simon Grelet, Laura A Link, Breege Howley, Clémence Obellianne, Viswanathan Palanisamy, Vamsi K Gangaraju, J Alan Diehl, Philip H Howe
The contribution of lncRNAs to tumour progression and the regulatory mechanisms driving their expression are areas of intense investigation. Here, we characterize the binding of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) to a nucleic acid structural element located in exon 12 of PNUTS (also known as PPP1R10) pre-RNA that regulates its alternative splicing. HnRNP E1 release from this structural element, following its silencing, nucleocytoplasmic translocation or in response to TGFβ, allows alternative splicing and generates a non-coding isoform of PNUTS...
September 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28803608/identification-of-simvastatin-regulated-targets-associated-with-jnk-activation-in-du145-human-prostate-cancer-cell-death-signaling
#16
Eun Joo Jung, Ky Hyun Chung, Choong Won Kim
The results of this study show that c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1), and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways...
September 2017: BMB Reports
https://www.readbyqxmd.com/read/28592492/heterogeneous-nuclear-ribonucleoprotein-k-inhibits-heat-shock-induced-transcriptional-activity-of-heat-shock-factor-1
#17
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 post-translationally 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...
August 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28570076/insight-into-the-complexity-of-the-i-motif-and-g-quadruplex-dna-structures-formed-in-the-kras-promoter-and-subsequent-drug-induced-gene-repression
#18
Christine E Kaiser, Natalie A Van Ert, Prashansa Agrawal, Reena Chawla, Danzhou Yang, Laurence H Hurley
Activating KRAS mutations frequently occur in pancreatic, colorectal, and lung adenocarcinomas. While many attempts have been made to target oncogenic KRAS, no clinically useful therapies currently exist. Most efforts to target KRAS have focused on inhibiting the mutant protein; a less explored approach involves targeting KRAS at the transcriptional level. The promoter element of the KRAS gene contains a GC-rich nuclease hypersensitive site with three potential DNA secondary structure-forming regions. These are referred to as the Near-, Mid-, and Far-regions, on the basis of their proximity to the transcription start site...
June 28, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28523741/comparative-membrane-proteomics-analyses-of-breast-cancer-cell-lines-to-understand-the-molecular-mechanism-of-breast-cancer-brain-metastasis
#19
COMPARATIVE STUDY
Wenjing Peng, Yu Zhang, Rui Zhu, Yehia Mechref
Breast cancer is the leading type of cancer in women. Breast cancer brain metastasis is currently considered an issue of concern among breast cancer patients. Membrane proteins play important roles in breast cancer brain metastasis, involving cell adhesion and penetration of blood-brain barrier. To understand the mechanism of breast cancer brain metastasis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in conjunction with enrichment of membrane proteins to analyze the proteomes from five different breast cancer and a brain cancer cell lines...
September 2017: Electrophoresis
https://www.readbyqxmd.com/read/28450158/the-erbb-family-and-androgen-receptor-signaling-are-targets-of%C3%A2-celecoxib-in-prostate-cancer
#20
Antonella Brizzolara, Roberto Benelli, Roberta Venè, Paola Barboro, Alessandro Poggi, Francesca Tosetti, Nicoletta Ferrari
Inflammation plays a central role in prostate cancer (PCa) development through significant crosstalk between the COX-2-ErbB family receptor network and androgen receptor (AR)-EGFR signaling pathways. The purpose of this work was to determine the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling pathway in androgen-dependent PCa cells and to provide a rationale for its beneficial use in chemopreventive strategies. Functional studies of Celecoxib activity were performed on LNCaP prostate cancer cells...
August 1, 2017: Cancer Letters
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