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https://www.readbyqxmd.com/read/29475060/lanatoside-c-inhibits-cell-proliferation-and-induces-apoptosis-through-attenuating-wnt-%C3%AE-catenin-c-myc-signaling-pathway-in-human-gastric-cancer-cell
#1
Yudong Hu, Kaikai Yu, Gang Wang, Depeng Zhang, Chaoji Shi, Yunhe Ding, Duo Hong, Dan Zhang, Huiqiong He, Lei Sun, Jun-Nian Zheng, Shuyang Sun, Feng Qian
Gastric cancer is the third common cause of cancer mortality in the world with poor prognosis and high recurrence due to lack of effective medicines. Our studies revealed that lanatoside C, a FDA-approved cardiac glycoside, had an anti-proliferation effect on different human cancer cell lines (MKN-45; SGC-7901; HN4; MCF-7; HepG2) and gastric cell lines MKN-45 and SGC-7901 were the most sensitive cell lines to lanatoside C. MKN-45 cells treated with lanatoside C showed cell cycle arrest at G2/M phase and inhibition of cell migration...
February 20, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29474981/physiological-functions-of-fbw7-in-cancer-and-metabolism
#2
REVIEW
Kouhei Shimizu, Naoe Taira Nihira, Hiroyuki Inuzuka, Wenyi Wei
FBW7 is one of the most well characterized F-box proteins that serve as substrate recognition subunits of SCF (Skp1-Cullin 1-F-box proteins) E3 ubiquitin ligase complexes. SCFFBW7 plays key roles in regulating cell cycle progression, differentiation, and stem cell maintenance largely through targeting a broad range of oncogenic substrates for proteasome-dependent degradation. The identification of an increasing number of FBW7 substrates for ubiquitination, and intensive in vitro and in vivo studies have revealed a network of signaling components controlled by FBW7 that contributes to metabolic regulation as well as its tumor suppressor role...
February 20, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29474739/mst1-2-kinases-modulate-glucose-uptake-for-osteoblast-differentiation-and-bone-formation
#3
Wenling Li, Yujie Deng, Bo Feng, Kingston King-Lun Mak
Bone formation and bone homeostasis are energy-expensive processes. How they are being regulated by energy needs are not completely understood. This is of high clinical importance as diabetic-induced bone loss is common where the underlying mechanisms are unclear. Here, we show that Mst1/2 are important regulators for glucose uptake during osteoblast differentiation. Genetically removal of both Mst1/2 kinases simultaneously in mice in early and mature osteoblasts respectively inhibits bone formation and bone remodeling...
February 23, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29474458/positive-cytoplasmic-uchl5-tumor-expression-in-gastric-cancer-is-linked-to-improved-prognosis
#4
Leena Arpalahti, Alli Laitinen, Jaana Hagström, Harri Mustonen, Arto Kokkola, Camilla Böckelman, Caj Haglund, Carina I Holmberg
Gastric cancer is the second most common cause of cancer-related mortality worldwide. Accurate prediction of disease progression is difficult, and new biomarkers for clinical use are essential. Recently, we reported that the proteasome-associated deubiquitinating enzyme UCHL5/Uch37 is a new prognostic marker in both rectal cancer and pancreatic ductal adenocarcinoma. Here, we have assessed by immunohistochemistry UCHL5 tumor expression in gastric cancer. The study cohort comprised 650 patients, who underwent surgery in Helsinki University Hospital, Finland, between 1983 and 2009...
2018: PloS One
https://www.readbyqxmd.com/read/29474435/sumo-polymeric-chains-are-involved-in-nuclear-foci-formation-and-chromatin-organization-in-trypanosoma-brucei-procyclic-forms
#5
Paula Ana Iribarren, Lucía Ayelén Di Marzio, María Agustina Berazategui, Javier Gerardo De Gaudenzi, Vanina Eder Alvarez
SUMOylation is a post-translational modification conserved in eukaryotic organisms that involves the covalent attachment of the small ubiquitin-like protein SUMO to internal lysine residues in target proteins. This tag usually alters the interaction surface of the modified protein and can be translated into changes in its biological activity, stability or subcellular localization, among other possible outputs. SUMO can be attached as a single moiety or as SUMO polymers in case there are internal acceptor sites in SUMO itself...
2018: PloS One
https://www.readbyqxmd.com/read/29473971/protacs-an-emerging-targeting-technique-for-protein-degradation-in-drug-discovery
#6
REVIEW
Shanshan Gu, Danrui Cui, Xiaoyu Chen, Xiufang Xiong, Yongchao Zhao
Proteolysis-targeting chimeric molecules (PROTACs) represent an emerging technique that is receiving much attention for therapeutic intervention. The mechanism is based on the inhibition of protein function by hijacking a ubiquitin E3 ligase for protein degradation. The hetero-bifunctional PROTACs contain a ligand for recruiting an E3 ligase, a linker, and another ligand to bind with the protein targeted for degradation. Thus, PROTACs have profound potential to eliminate "undruggable" protein targets, such as transcription factors and non-enzymatic proteins, which are not limited to physiological substrates of the ubiquitin-proteasome system...
February 23, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29473060/the-life-of-proteins-under-mechanical-force
#7
REVIEW
Jörg Schönfelder, Alvaro Alonso-Caballero, David De Sancho, Raul Perez-Jimenez
Although much of our understanding of protein folding comes from studies of isolated protein domains in bulk, in the cellular environment the intervention of external molecular machines is essential during the protein life cycle. During the past decade single molecule force spectroscopy techniques have been extremely useful to deepen our understanding of these interventional molecular processes, as they allow for monitoring and manipulating mechanochemical events in individual protein molecules. Here, we review some of the critical steps in the protein life cycle, starting with the biosynthesis of the nascent polypeptide chain in the ribosome, continuing with the folding supported by chaperones and the translocation into different cell compartments, and ending with proteolysis in the proteasome...
February 23, 2018: Chemical Society Reviews
https://www.readbyqxmd.com/read/29472944/roles-of-e3-ubiquitin-ligases-in-nuclear-protein-homeostasis-during-plant-stress-responses
#8
REVIEW
Irene Serrano, Laura Campos, Susana Rivas
Ubiquitination, the reversible protein conjugation with ubiquitin (Ub), is a post-translational modification that enables rapid and specific cellular responses to stimuli without requirement of de novo protein synthesis. Although ubiquitination also displays non-proteolytic functions, it often acts as a signal for selective protein degradation through the ubiquitin-proteasome system (UPS). In plants, it has become increasingly apparent that the UPS is a central regulator of many key cellular and physiological processes, including responses to biotic and abiotic stresses...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29472861/1-2-3-4-6-penta-o-galloyl-beta-d-glucopyranoside-inhibits-proliferation-of-multiple-myeloma-cells-accompanied-with-suppression-of-myc-expression
#9
Duurenjargal Tseeleesuren, Rajni Kant, Chia-Hung Yen, Hui-Hua Hsiao, Yi-Ming A Chen
Multiple myeloma (MM) still remains an incurable disease, therefore discovery of novel drugs boosts the therapeutics for MM. The natural compound 1,2,3,4,6-Penta- O -galloyl-beta-D-glucopyranoside (PGG) has been shown to exhibit antitumor activities against various cancer cells. Here, we aim to evaluate antitumor effects of PGG on MM cell lines. PGG inhibited the growth of three different MM cell lines in a dose- and time-dependent manner. Cell cycle analysis revealed that PGG treatment caused cell cycle arrest in G1 phase...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29472714/oncogene-induced-senescence-mediated-by-c-myc-requires-usp10-dependent-deubiquitination-and-stabilization-of-p14arf
#10
Aram Ko, Su Yeon Han, Chel Hun Choi, Hanbyoul Cho, Min-Sik Lee, Soo-Youl Kim, Joon Seon Song, Kyeong-Man Hong, Han-Woong Lee, Stephen M Hewitt, Joon-Yong Chung, Jaewhan Song
Oncogene-induced senescence (OIS) is a critical tumor-suppressor mechanism, which prevents hyper-proliferation and transformation of cells. c-Myc promotes OIS through the transcriptional activation of p14ARF followed by p53 activation. Although the oncogene-mediated transcriptional regulation of p14ARF has been well addressed, the post-translational modification of p14ARF regulated by oncogenic stress has yet to be investigated. Here, we found that c-Myc increased p14ARF protein stability by inducing the transcription of ubiquitin-specific protease 10 (USP10)...
February 22, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29472364/pseudo-dubs-as-allosteric-activators-and-molecular-scaffolds-of-protein-complexes
#11
REVIEW
Miriam Walden, Safi Kani Masandi, Krzysztof Pawłowski, Elton Zeqiraj
The ubiquitin (Ub) proteasome system and Ub signalling networks are crucial to cell biology and disease development. Deubiquitylases (DUBs) control cell signalling by removing mono-Ub and polyubiquitin chains from substrates. DUBs take part in almost all processes that regulate cellular life and are frequently dysregulated in disease. We have catalogued 99 currently known DUBs in the human genome and sequence conservation analyses of catalytic residues suggest that 11 lack enzyme activity and are classed as pseudo-DUBs...
February 22, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29472293/degradation-of-the-endoplasmic-reticulum-anchored-transcription-factor-myrf-by-the-ubiquitin-ligase-scf-fbxw7-in-a-manner-dependent-on-the-kinase-gsk-3
#12
Shogo Nakayama, Kanae Yumimoto, Atsuki Kawamura, Keiichi I Nakayama
The ubiquitin-proteasome system regulates the abundance of many cellular proteins by mediating their targeted degradation. We previously developed a method-differential proteomics-based identification of ubiquitylation substrates (DiPIUS)-for the comprehensive identification of substrates for a given F-box protein subunit of SCF-type ubiquitin ligases. We have now applied DiPIUS to the F-box protein Fbxw7 in three cell lines (mHepa, Neuro2A, and C2C12) and thereby identified myelin regulatory factor (MyRF)-an endoplasmic reticulum-anchored transcription factor that is essential for myelination of nerves in the central nervous system-as a candidate substrate of Fbxw7 specifically in mHepa cells...
February 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29472278/siamese-related1-is-regulated-post-translationally-and-participates-in-repression-of-leaf-growth-under-moderate-drought
#13
Marieke Dubois, Katia Selden, Alexis Bediée, Gaëlle Rolland, Nicolas Baumberger, Sandra Noir, Lien Bach, Geneviève Lamy, Christine Granier, Pascal Genschik
The plant cell cycle is tightly regulated by factors that integrate endogenous cues and environmental signals to adapt plant growth to changing conditions. Under drought, cell division in young leaves is blocked by an active mechanism, reducing the evaporative surface and conserving energy resources. The molecular function of cyclin-dependent kinase-inhibitory proteins (CKIs) in regulating the cell cycle has already been well studied, but little is known about their involvement in cell cycle regulation under adverse growth conditions...
February 22, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29469592/ixazomib-in-the-management-of-relapsed-multiple-myeloma
#14
Cyrille Touzeau, Philippe Moreau
The development of proteasome inhibitors contributed to the dramatic life expectancy improvement observed in myeloma patients over the past decades. Ixazomib is a boron-containing selective and reversible proteasome inhibitor that demonstrated antimyeloma activity with excellent safety profile. Ixazomib is the first orally available proteasome inhibitor approved in combination with lenalidomide and dexamethasone for the treatment of myeloma patients who received at least one prior therapy. The present review addresses the current knowledge regarding the clinical use of ixazomib in relapsed myeloma patients...
February 22, 2018: Future Oncology
https://www.readbyqxmd.com/read/29468963/nf-%C3%AE%C2%BAb-ikk%C3%AE-pathway-as-a-target-for-drug-development-realities-challenges-and-perspectives
#15
Rosana H C N Freitas, Carlos A M Fraga
BACKGROUND: Nuclear factor κB (NF-κB) comprises a family of proteins that act as transcription factors promoting the expression of many genes. Activation of NF-κB biochemical cascades is associated with the regulation of innate and adaptive immune responses and inflammation, among other physiological responses. However, genetic abnormalities and continuous stimulation of the NF-κB-IKKβ pathway are directly related to many types of inflammatory and autoimmune diseases, as well as to the genesis and survival of tumor cells...
February 19, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29467964/correction-co-targeting-translation-and-proteasome-rapidly-kills-colon-cancer-cells-with-mutant-ras-raf-via-er-stress
#16
Xiangyun Li, Mei Li, Hang Ruan, Wei Qiu, Xiang Xu, Zhang Lin, Jian Yu
[This corrects the article DOI: 10.18632/oncotarget.14063.].
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29467657/effects-of-sodium-and-amino-acid-substrate-availability-upon-the-expression-and-stability-of-the-snat2-slc38a2-amino-acid-transporter
#17
Thorsten M Hoffmann, Emma Cwiklinski, Dinesh S Shah, Clare Stretton, Russell Hyde, Peter M Taylor, Harinder S Hundal
The SNAT2 (SLC38A2) System A amino acid transporter mediates Na+ -coupled cellular uptake of small neutral α-amino acids (AAs) and is extensively regulated in response to humoral and nutritional cues. Understanding the basis of such regulation is important given that AA uptake via SNAT2 has been linked to activation of mTORC1; a major controller of many important cellular processes including, for example, mRNA translation, lipid synthesis, and autophagy and whose dysregulation has been implicated in the development of cancer and conditions such as obesity and type 2 diabetes...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29467282/proteomic-profiling-of-vcp-substrates-links-vcp-to-k6-linked-ubiquitylation-and-c-myc-function
#18
Jan B Heidelberger, Andrea Voigt, Marina E Borisova, Giuseppe Petrosino, Stefanie Ruf, Sebastian A Wagner, Petra Beli
Valosin-containing protein (VCP) is an evolutionarily conserved ubiquitin-dependent ATPase that mediates the degradation of proteins through the ubiquitin-proteasome pathway. Despite the central role of VCP in the regulation of protein homeostasis, identity and nature of its cellular substrates remain poorly defined. Here, we combined chemical inhibition of VCP and quantitative ubiquitin remnant profiling to assess the effect of VCP inhibition on the ubiquitin-modified proteome and to probe the substrate spectrum of VCP in human cells...
February 21, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29467225/the-transmembrane-protein-tmepai-induces-myeloma-cell-apoptosis-by-promoting-degradation-of-the-c-maf-transcription-factor
#19
Yanyun Du, Yan Liu, Yujia Xu, Jiaxiang Juan, Zubin Zhang, Zhuan Xu, Biyin Cao, Qi Wang, Yuanying Zeng, Xinliang Mao
Transmembrane prostate androgen-induced protein (TMEPAI, also called prostate transmembrane protein, androgen induced 1 [PMEPA1]), is a type I transmembrane (TM) protein, but its cellular function is largely unknown. Here, studying factors influencing the stability of c-Maf, a critical transcription factor in multiple myeloma (MM), we found that TMEPAI induced c-Maf degradation. We observed that TMEPAI recruited neural precursor cell expressed, developmentally down-regulated 4 (NEDD4), a WW domain-containing ubiquitin ligase, to c-Maf, leading to its degradation through the proteasomal pathway...
February 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29465983/targeting-the-proteostasis-network-for-mycobacterial-drug-discovery
#20
Tania J Lupoli, Julien Vaubourgeix, Kristin Burns-Huang, Ben Gold
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the world's deadliest infectious diseases and urgently requires new antibiotics to treat drug-resistant strains and to decrease the duration of therapy. During infection, Mtb encounters numerous stresses associated with host immunity, including hypoxia, reactive oxygen and nitrogen species, mild acidity, nutrient starvation, and metal sequestration and intoxication. The Mtb proteostasis network, composed of chaperones, proteases, and a eukaryotic-like proteasome, provides protection from stresses and chemistries of host immunity by maintaining the integrity of the mycobacterial proteome...
February 21, 2018: ACS Infectious Diseases
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