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Regulated Alternative Translocation

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https://www.readbyqxmd.com/read/28543886/human-hairless-protein-roles-in-skin-hair-and-emerging-connections-to-brain-and-other-cancers
#1
Anas Maatough, G Kerr Whitfield, Lemlem Brook, David Hsieh, Patricia Palade, Jui-Cheng Hsieh
The mammalian hairless protein (HR) is a 130 kDa nuclear transcription factor that is essential for proper skin and hair follicle function. Previous studies have focused on the role of HR in skin maintenance and hair cycling. However, hairless gene (HR) is also expressed in brain and other tissues, where its role remains poorly understood. HR has been reported to contain functional domains that potentially serve in DNA binding, histone demethylation, nuclear translocation signal, and protein-protein interactions...
May 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28513634/mitochondria-targeted-platinum-ii-complexes-dual-inhibitory-activities-on-tumor-cell-proliferation-and-migration-invasion-via-intracellular-trafficking-of-%C3%AE-catenin
#2
Jingling Li, Xiaoli He, Yeling Zou, Dandan Chen, Liecheng Yang, Jiaming Rao, Huabing Chen, Michael C W Chan, Lin Li, Zhengqing Guo, Leshuai W Zhang, Chunying Chen
Mitochondria-targeted therapy is an alternative strategy for cancer therapy and may overcome the problems of metastasis and drug resistance that usually occur in conventional treatment. In this work, we demonstrate the mitochondria-targeted delivery of a cationic cyclometalated platinum(ii) complex, PIP-platin, in cancer cells. PIP-platin showed selective delivery and accumulation in the mitochondria and exhibited toxicity against a variety of tumor cell lines. The mitochondria were disrupted by PIP-platin, along with the generation of reactive oxygen species, depolarization of mitochondrial membrane potential, release of cytochrome c and necrosis...
May 17, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28512350/mechanisms-of-action-and-regulation-of-atp-dependent-chromatin-remodelling-complexes
#3
REVIEW
Cedric R Clapier, Janet Iwasa, Bradley R Cairns, Craig L Peterson
Cells utilize diverse ATP-dependent nucleosome-remodelling complexes to carry out histone sliding, ejection or the incorporation of histone variants, suggesting that different mechanisms of action are used by the various chromatin-remodelling complex subfamilies. However, all chromatin-remodelling complex subfamilies contain an ATPase-translocase 'motor' that translocates DNA from a common location within the nucleosome. In this Review, we discuss (and illustrate with animations) an alternative, unifying mechanism of chromatin remodelling, which is based on the regulation of DNA translocation...
May 17, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28503306/the-drive-to-generate-multiple-forms-of-oncogenic-cyclin-d1-transcripts-in-mantle-cell-lymphoma
#4
EDITORIAL
Chioniso Patience Masamha
Alternative polyadenylation is a rapidly emerging form of gene regulation, which in its simplest form, enables the generation of mRNA transcripts that code for the same protein but have 3'UTRs of different lengths and regulatory content. For oncogenes, shorter 3'UTRs would be preferred as a mechanism to evade miRNA regulation. The shortening of the 3'UTR of cyclin D1 in mantle cell lymphoma offers provocative insights into this process. Patient samples have revealed that 3'UTR shortening may occur due to mutations, or translocations that result in the generation of a chimeric 3'UTR...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28467182/roles-of-silent-information-regulator-1-serine-arginine-rich-splicing-factor-10-lipin-1-axis-in-the-pathogenesis-of-alcohol-fatty-liver-disease
#5
Yuanyuan Li, Junying Zhou
Alcohol exposure is a major reason of morbidity and mortality all over the world, with much of detrimental consequences attributing to alcoholic liver disease (ALD). With the continued ethanol consumption, alcoholic fatty liver disease (AFLD, the earliest and reversible form of ALD) can further develop to more serious forms of alcoholic liver damage, including alcoholic steatohepatitis, fibrosis/cirrhosis, and even eventually progress to hepatocellular carcinoma and liver failure. Furthermore, cell trauma, inflammation, oxidative stress, regeneration, and bacterial translocation are crucial promoters of ethanol-mediated liver lesions...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28465491/discovery-and-characterization-of-small-molecules-targeting-the-dna-binding-ets-domain-of-erg-in-prostate-cancer
#6
Miriam S Butler, Mani Roshan-Moniri, Michael Hsing, Desmond Lau, Ari Kim, Paul Yen, Marta Mroczek, Mannan Nouri, Scott Lien, Peter Axerio-Cilies, Kush Dalal, Clement Yau, Fariba Ghaidi, Yubin Guo, Takeshi Yamazaki, Sam Lawn, Martin E Gleave, Cheryl Y Gregory-Evans, Lawrence P McIntosh, Michael E Cox, Paul S Rennie, Artem Cherkasov
Genomic alterations involving translocations of the ETS-related gene ERG occur in approximately half of prostate cancer cases. These alterations result in aberrant, androgen-regulated production of ERG protein variants that directly contribute to disease development and progression. This study describes the discovery and characterization of a new class of small molecule ERG antagonists identified through rational in silico methods. These antagonists are designed to sterically block DNA binding by the ETS domain of ERG and thereby disrupt transcriptional activity...
April 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28447783/real-time-detection-reveals-responsive-cotranscriptional-formation-of-persistent-intramolecular-dna-and-intermolecular-dna-rna-hybrid-g-quadruplexes-stabilized-by-r-loop
#7
Yang Zhao, Jia-Yu Zhang, Zong-Yu Zhang, Tan-Jun Tong, Yu-Hua Hao, Zheng Tan
G-quadruplex (GQ) structures are implicated in important physiological and pathological processes. Millions of GQ-forming motifs are enriched near transcription start sites (TSSs) of animal genes. Transcription can induce the formation of GQs, which in turn regulate transcription. The kinetics of the formation and persistence of GQs in transcription is crucial for the role they play but has not yet been explored. We established a method based on the fluorescence resonance energy transfer (FRET) technique to monitor in real-time the cotranscriptional formation and post-transcriptional persistence of GQs in DNA...
May 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28408318/regulation-of-agr2-expression-via-3-utr-shortening
#8
Eva Matoulkova, Lucia Sommerova, Michal Pastorek, Borivoj Vojtesek, Roman Hrstka
One recently discussed general mechanism affecting gene expression is 3'-untranslated region (3'UTR) length. Events such as shortening, translocation or loss of 3'UTRs are observed within oncogenes and are proposed to associate with increased expression. Thus, increased efforts are being made to understand constitutive and differential transcript 3'end formation. Investigation of AGR2 mRNA revealed a direct impact of its 3'UTR length on AGR2 expression. In silico analyses identified several regulatory sequences within the distal part of AGR2 mRNA that may regulate 3'UTR length and associated protein levels...
April 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28349780/ganoderic-acid-targeting-nuclear-factor-erythroid-2-related-factor-2-in-lung-cancer
#9
Balraj Singh Gill, Sanjeev Kumar, Navgeet
Lung cancer causes huge mortality worldwide, and targeting new pathway may provide an alternative in modulating signaling in cancer. Nuclear factor erythroid 2-related factor 2 is the major regulator of endogenous and exogenous stress by activating numerous antioxidant genes critical in cancer, Alzheimer's, Parkinson's, and inflammatory bowel diseases. Ganoderic acid is a triterpene from basiodiomycetes fungus Ganoderma lucidum with numerous therapeutic effects. In this study, ganoderic acid and its 50 isomers and natural activators were docked by receptor-based molecular docking using Maestro 9...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28340354/mechanism-of-substrate-translocation-in-an-alternating-access-transporter
#10
Naomi R Latorraca, Nathan M Fastman, A J Venkatakrishnan, Wolf B Frommer, Ron O Dror, Liang Feng
Transporters shuttle molecules across cell membranes by alternating among distinct conformational states. Fundamental questions remain about how transporters transition between states and how such structural rearrangements regulate substrate translocation. Here, we capture the translocation process by crystallography and unguided molecular dynamics simulations, providing an atomic-level description of alternating access transport. Simulations of a SWEET-family transporter initiated from an outward-open, glucose-bound structure reported here spontaneously adopt occluded and inward-open conformations...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28321271/parkin-in-cancer-mitophagy-related-unrelated-tasks
#11
EDITORIAL
Nabil Eid, Yoichi Kondo
Dysfunctional mitochondria may produce excessive reactive oxygen species, thus inducing DNA damage, which may be oncogenic if not repaired. As a major role of the PINK1-Parkin pathway involves selective autophagic clearance of damaged mitochondria via a process termed mitophagy, Parkin-mediated mitophagy may be a tumor-suppressive mechanism. As an alternative mechanism for tumor inhibition beyond mitophagy, Parkin has been reported to have other oncosuppressive functions such as DNA repair, negative regulation of cell proliferation and stimulation of p53 tumor suppressor function...
March 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28284859/molecular-mechanisms-of-3-3-4-4-5-pentachlorobiphenyl-induced-epithelial-mesenchymal-transition-in-human-hepatocellular-carcinoma-cells
#12
Li Song, Linlin Guo, Zhuoyu Li
Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs). Many studies have found a positive association between the progression of hepatocellular carcinoma (HCC) and PCBs exposure. However, the influence of PCBs on epithelial-mesenchymal transition (EMT) of HCC remains to be unclear. In this study, we explored the effect of PCB126 on EMT in HCC cells and its underlying mechanisms. The data showed that PCB126, exposing both Bel-7402 and SMMC-7721 cells for 48h, promoted EMT that was demonstrated by E-cadherin repression, up-regulation of N-cadherin and vimentin, and morphological alteration...
May 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28215533/plastid-protein-targeting-preprotein-recognition-and-translocation
#13
P Chotewutmontri, K Holbrook, B D Bruce
Eukaryotic organisms are defined by their endomembrane system and various organelles. The membranes that define these organelles require complex protein sorting and molecular machines that selectively mediate the import of proteins from the cytosol to their functional location inside the organelle. The plastid possibly represents the most complex system of protein sorting, requiring many different translocons located in the three membranes found in this organelle. Despite having a small genome of its own, the vast majority of plastid-localized proteins is nuclear encoded and must be posttranslationally imported from the cytosol...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28068633/polyphenol-rich-ethanolic-extract-from-boerhavia-diffusa-l-mitigates-angiotensin-ii-induced-cardiac-hypertrophy-and-fibrosis-in-rats
#14
Prathapan A, Mathews V Varghese, Abhilash S, Salin Raj P, Anil K Mathew, Anupama Nair, R Harikumaran Nair, Raghu K G
Boerhavia diffusa is a renowned edible medicinal plant extensively used against different ailments including heart diseases in the traditional system of medicine in several countries. The present study aims to evaluate the therapeutic efficacy of ethanolic extract of Boerhavia diffusa (BDE) on cardiac hypertrophy and fibrosis induced by angiotensin II (Ang II) in male wistar rats and to identify the active components present in it. A substantial increase of hypertrophy markers such as cardiac mass index, concentration of ANP and BNP, cardiac injury markers like CK-MB, LDH and SGOT, has been observed in hypertrophied groups whereas BDE treatment attenuated these changes when compared to hypertrophied rats...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28055972/integrative-genomic-and-transcriptomic-analysis-for-pinpointing-recurrent-alterations-of-plant-homeodomain-genes-and-their-clinical-significance-in-breast-cancer
#15
Huimei Yu, Yuanyuan Jiang, Lanxin Liu, Wenqi Shan, Xiaofang Chu, Zhe Yang, Zeng-Quan Yang
A wide range of the epigenetic effectors that regulate chromatin modification, gene expression, genomic stability, and DNA repair contain structurally conserved domains called plant homeodomain (PHD) fingers. Alternations of several PHD finger-containing proteins (PHFs) due to genomic amplification, mutations, deletions, and translocations have been linked directly to various types of cancer. However, little is known about the genomic landscape and the clinical significance of PHFs in breast cancer. Hence, we performed a large-scale genomic and transcriptomic analysis of 98 PHF genes in breast cancer using TCGA and METABRIC datasets and correlated the recurrent alterations with clinicopathological features and survival of patients...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28039561/functional-characterization-of-tomato-membrane-bound-nac-transcription-factors
#16
Payel Bhattacharjee, Rohit Das, Arunava Mandal, Pallob Kundu
Genome-wide analysis was carried out to identify and analyze differential expression pattern of tomato membrane bound NAC transcription factors (SlNACMTFs) during stresses. Two biotic-stress-related SlNACMTFs have been characterized to elucidate their regulatory function. NAC transcription factors are known regulators of stress-related gene expression. As Stresses are perceived and transmitted by membrane-bound proteins, functional characterization of membrane-associated NAC transcription factors in tomato can reveal valuable insight about membrane-mediated stress-signalling...
March 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/27939598/alternative-roles-for-oxidized-mcs-and-tets
#17
REVIEW
Luisa Cimmino, Iannis Aifantis
Ten-eleven-translocation (TET) proteins oxidize 5-methylcytosine (5mC) to form stable or transient modifications (oxi-mCs) in the mammalian genome. Genome-wide mapping and protein interaction studies have shown that 5mC and oxi-mCs have unique distribution patterns and alternative roles in gene expression. In addition, oxi-mCs may interact with specific chromatin regulators, transcription factors and DNA repair proteins to maintain genomic integrity or alter DNA replication and transcriptional elongation rates...
December 7, 2016: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/27933067/peptide-idr-1002-inhibits-nf-%C3%AE%C2%BAb-nuclear-translocation-by-inhibition-of-i%C3%AE%C2%BAb%C3%AE-degradation-and-activates-p38-erk1-2-msk1-dependent-creb-phosphorylation-in-macrophages-stimulated-with-lipopolysaccharide
#18
Alejandro Huante-Mendoza, Octavio Silva-García, Javier Oviedo-Boyso, Robert E W Hancock, Víctor M Baizabal-Aguirre
The inflammatory response is a critical molecular defense mechanism of the innate immune system that mediates the elimination of disease-causing bacteria. Repair of the damaged tissue, and the reestablishment of homeostasis, must be accomplished after elimination of the pathogen. The innate defense regulators (IDRs) are short cationic peptides that mimic natural host defense peptides and are effective in eliminating pathogens by enhancing the activity of the immune system while controlling the inflammatory response...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27888447/the-regulation-of-the-mitochondrial-apoptotic-pathway-by-glucocorticoid-receptor-in-collaboration-with-bcl-2-family-proteins-in-developing-t-cells
#19
Lilla Prenek, Ferenc Boldizsár, Réka Kugyelka, Emese Ugor, Gergely Berta, Péter Németh, Timea Berki
Glucocorticoids (GC) are important in the regulation of selection and apoptosis of CD4(+)CD8(+) double-positive (DP) thymocytes. The pronounced GC-sensitivity of DP thymocytes, observed earlier, might be due to the combination of classical (genomic) and alternative (non-genomic) glucocorticoid receptor (GR) signaling events modifying activation or apoptotic pathways. In particular, the previously demonstrated mitochondrial translocation of activated GR in DP thymocytes offered a fascinating explanation for their pronounced GC-induced apoptosis sensitivity...
February 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27814612/mirnas-as-drivers-of-tmprss2-erg-negative-prostate-tumors-in-african-american-men
#20
Clayton Yates, Mark D Long, Moray J Campbell, Lara Sucheston-Campbell
African Americans (AAs) who have PCa typically have more aggressive disease and make up a disproportionate number of the disease deaths, relative to European Americans (EAs). TMPRSS2 translocations, a common event in EA patients, are exploited in diagnostic and prognostic settings, whereas they are diminished in frequency in AA men. Thus, these patients with TMPRSS2 fusion-negative disease represent an under-investigated patient group. We propose that epigenetic events are a significant and alternative driver of aggressive disease in fusion-negative PCa...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
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