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BMB Reports

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https://www.readbyqxmd.com/read/28803610/two-distinct-nodes-of-translational-inhibition-in-the-integrated-stress-response
#1
Hyung Don Ryoo, Deepika Vasudevan
The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated eIF2α kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor eIF2α...
August 14, 2017: BMB Reports
https://www.readbyqxmd.com/read/28803609/comic-the-hidden-dynamics-of-mitochondrial-inner-compartments
#2
Bongki Cho, Woong Sun
Mitochondria have evolutionarily, functionally and structurally distinct outer- (OMM) and inner-membranes (IMM). Thus, mitochondrial morphology is controlled by independent but coordinated activity of fission and fusion of the OMM and IMM. Constriction and division of the OMM are mediated by endocytosis-like machineries, which include dynamin-related protein 1 with additional cytosolic vesicle scissoring machineries such as actin filament and Dynamin 2. However, structural alteration of the IMM during mitochondrial division has been poorly understood...
August 14, 2017: BMB Reports
https://www.readbyqxmd.com/read/28803608/identification-of-simvastatin-regulated-targets-associated-with-jnk-activation-in-du145-human-prostate-cancer-cell-death-signaling
#3
Eun Joo Jung, Ky Hyun Chung, Choong Won Kim
In this study, our results showed that the 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...
August 11, 2017: BMB Reports
https://www.readbyqxmd.com/read/28768566/dead-cell-phagocytosis-and-innate-immune-checkpoint
#4
Kyoung Wan Yoon
Human body are losing several billions of cells every day. When cells are dying in vivo, the corpse of dead cell are not remained uncleared. Dead cells are efficiently recognized and cleared by multiple types of neighboring phagocytes. In the initial researches studying cell death, molecular mechanisms regulating cell death are more focused and the end corpse are simply considered as cellular debris. However, it has been revealed that various biological influences after cell death are important for the followed immune regulations...
August 3, 2017: BMB Reports
https://www.readbyqxmd.com/read/28768565/caspase-2-mediates-triglyceride-tg-induced-macrophage-cell-death
#5
Jaewon Lim, Sung Hoon Kim, Hyun-Kyung Kim, Ki-Jong Rhee, Yoon Suk Kim
Triglyceride (TG) accumulation causes macrophage cell death, which affects the development of atherosclerosis. Here, we examined whether caspase-2 is implicated in TG-induced macrophage cell death. We found that caspase-2 activity is increased in TG-treated THP-1 macrophages, and that inhibition of caspase-2 activity drastically inhibits TG-induced cell death. We previously reported that TG-induced macrophage death is triggered by caspase-1, and thus investigated the relationship between casapse-2 and caspase-1 in TG-induced macrophage cell death...
August 3, 2017: BMB Reports
https://www.readbyqxmd.com/read/28760197/transforming-growth-factor-%C3%AE-1-enhances-adhesion-of-endometrial-cells-to-mesothelium-by-regulating-integrin-expression
#6
Hee-Jung Choi, Mi-Ju Park, Bo-Sung Kim, Hee-Jin Choi, Bosun Joo, Kyu Sup Lee, Jung-Hye Choi, Tae-Wook Chung, Ki-Tae Ha
Interestingly, transforming growth factor β1 (TGF-β1) expression was higher in endometriotic epithelial cells than in normal endometrial cells. The adhesion efficiency of endometriotic epithelial cells to mesothelial cells was also higher than that of normal endometrial cells. Moreover, TGF-β1 directly induced the adhesion of endometrial cells to mesothelial cells through the regulation of integrin of αV, α6, β1, and β4 via the activation of the TGF-β1/TGF-βRI/Smad2 signaling pathway. Conversely, the adhesion of TGF-β1-stimulated endometrial cells to mesothelial cells was clearly reduced following treatment with neutralizing antibodies against specific TGF-β1-mediated integrins αV, β1, and β4 on the endometrial cell membrane...
August 1, 2017: BMB Reports
https://www.readbyqxmd.com/read/28760196/effects-of-pep-1-fk506bp-on-cyst-formation-in-polycystic-kidney-disease
#7
Hyo Sang Jo, Won Sik Eum, Eun Young Park, Je Young Ko, Do Yeon Kim, Dae Won Kim, Min Jea Shin, Ora Son, Su Bin Cho, Jung Hwan Park, Chi Hern Lee, Eun Ji Yeo, Hyeon Ji Yeo, Yeon Joo Choi, Jong Kyu Youn, Sung-Woo Cho, Jinseu Park, Jong Hoon Park, Soo Young Choi
Polycystic kidney disease (PKD) is one of the most common inherited disorders, whereby progressive cyst formation in the kidney leads to renal failure. FK506 binding protein 12 (FK506BP) is an immunophilin protein which performs multiple functions including regulation of cell signaling and survival. In this study, we determined the roles of PEP-1-FK506BP on cell proliferation and cyst formation in PKD cells. Purified PEP-1-FK506BP transduced into PKD cells and markedly inhibited cell proliferation. Also, PEP-1-FK506BP drastically inhibited the expression levels of p-Akt, p-p70S6K, p-mTOR, and p-ERK in PKD cells...
July 28, 2017: BMB Reports
https://www.readbyqxmd.com/read/28712389/rescuing-p53-from-mdm2-by-intrinsically-unfolded-sumo-protease-4
#8
Do-Hyoung Kim, Chewook Lee, Bom Kim, Si-Hyung Lee, Kyou-Hoon Han
Many intrinsically unstructured/unfolded proteins (IUPs) contain transient local secondary structures even though they are "unstructured" in a tertiary sense. These local secondary structures are named "pre-structured motifs (PreSMos)" and in fact are the specificity determinants for IUP-target binding, i.e., the active sites in IUPs. Using high-resolution NMR we have delineated a PreSMo active site in the intrinsically unfolded mid-domain (residues 201-300) of SUMO-specific protease 4 (SUSP4). This 29-residue motif which we termed a p53 rescue motif can protect p53 from mdm2 quenching by binding to the p53-helix binding pocket in mdm2(3-109)...
July 17, 2017: BMB Reports
https://www.readbyqxmd.com/read/28712388/ring-e3-ligases-key-regulatory-elements-are-involved-in-abiotic-stress-responses-in-plants
#9
Seok Keun Cho, Moon Young Ryu, Jong Hum Kim, Jeong Soo Hong, Tae Rin Oh, Woo Taek Kim, Seong Wook Yang
Plants are constantly exposed to a variety of abiotic stresses, such as drought, heat, cold, flood, and salinity. To survive under such unfavorable conditions, plants have evolutionarily developed their own resistant-mechanisms. For several decades, many studies have clarified specific stress response pathways of plants through various molecular and genetic studies. In particular, it was recently discovered that ubiquitin proteasome system (UPS), a regulatory mechanism for protein turn over, is greatly involved in the stress responsive pathways...
July 17, 2017: BMB Reports
https://www.readbyqxmd.com/read/28712387/srsf2-directly-inhibits-intron-splicing-to-suppresses-cassette-exon-inclusion
#10
Heegyum Moon, Sunghee Cho, Tiing Jen Loh, Ha Na Jang, Yongchao Liu, Namjeong Choi, Jagyeong Oh, Jiyeon Ha, Jianhua Zhou, Sungchan Cho, Dong-Eun Kim, Michael B Ye, Xuexiu Zheng, Haihong Shen
SRSF2, a Serine-Arginine rich (SR) protein, is a splicing activator that mediates exon inclusion and exclusion events equally well. Here we show SRSF2 directly suppresses intron splicing to suppress cassette exon inclusion in SMN pre-mRNA. Through a serial mutagenesis, we demonstrate that a 10 nt RNA sequence surrounding the branch-point (BP), is important for SRSF2-mediated inhibition of cassette exon inclusion through directly interacting with SRSF2. We conclude that SRSF2 inhibits intron splicing to promote exon exclusion...
July 17, 2017: BMB Reports
https://www.readbyqxmd.com/read/28712386/neuropeptide-y-improves-cisplatin-induced-bone-marrow-dysfunction-without-blocking-chemotherapeutic-efficacy-in-a-cancer-mouse-model
#11
Min Hee Park, In Kyung Jung, Woo-Kie Min, Jin Ho Choi, Gyu Man Kim, Hee Kyung Jin, Jae-Sung Bae
Cisplatin is the most effective and widely used chemotherapeutic agent for many types of cancer. Unfortunately, its clinical use is limited by its adverse effects, notably bone marrow suppression leading to abnormal hematopoiesis. We previously revealed that neuropeptide Y (NPY) is responsible for the maintenance of hematopoietic stem cell (HSC) function by protecting the sympathetic nervous system (SNS) fibers survival from chemotherapy-induced bone marrow impairment. Here, we show the NPY-mediated protective effect against bone marrow dysfunction due to cisplatin in an ovarian cancer mouse model...
July 17, 2017: BMB Reports
https://www.readbyqxmd.com/read/28683851/survival-of-apc-mutant-colorectal-cancer-cells-requires-interaction-between-tankyrase-and-a-thiol-peroxidase-peroxiredoxin-ii
#12
Dong Hoon Kang, Joanna H S Lee, Sang Won Kang
Overexpression of mammalian 2-Cys peroxiredoxin (Prx) enzymes is observed in most cancer tissues. Nevertheless, their specific role in colorectal cancer progression has yet to be fully elucidated. Here, a novel molecular mechanism by which PrxII/TNKS interaction mediates survival of APC-mutant CRC cells was explored. In mice with inactivating APC mutation, a model of spontaneous intestinal tumorigenesis, deletion of PrxII reduces intestinal adenomatous polyposis and thereby increases survival. In APC mutation-derived human CRC cells, PrxII depletion hinders the PARP-dependent Axin1 degradation through TNKS inactivation...
July 7, 2017: BMB Reports
https://www.readbyqxmd.com/read/28683850/suppression-of-sirt2-and-altered-acetylation-status-of-human-pluripotent-stem-cells-possible-link-to-metabolic-switch-during-reprogramming
#13
Ok-Seon Kwon, Min-Joon Han, Hyuk-Jin Cha
Primed human pluripotent stem cells (hPSCs) are highly dependent on glycolysis rather than oxidative phosphorylation, which is similar to the metabolic switch that occurs in cancer cells. However, the molecular mechanisms that underlie this metabolic reprogramming in hPSCs and its relevance to pluripotency remain unclear. Cha et al. (2017) recently revealed that downregulation of SIRT2 by miR-200c enhances acetylation of glycolytic enzymes and glycolysis, which in turn facilitates cellular reprogramming, suggesting that SIRT2 is a key enzyme linking the metabolic switch and pluripotency in hPSCs...
July 7, 2017: BMB Reports
https://www.readbyqxmd.com/read/28683849/large-scale-human-yeast-genetic-interaction-for-construction-of-disease-network-systematic-discovery-of-multiple-drug-targets
#14
Kyoungho Suk
A novel approach has been used to identify functional interactions relevant to human disease. Using high-throughput human-yeast genetic interaction screens, a first draft of disease interactome was obtained. This was achieved by firstly searching for candidate human disease genes that confer toxicity in yeast, and secondly identifying modulators of this toxicity. The study found potentially disease-relevant interactions by analyzing the network of functional interactions and focusing on genes implicated in amyotrophic lateral sclerosis (ALS), for instance...
July 7, 2017: BMB Reports
https://www.readbyqxmd.com/read/28648147/functional-roles-of-ctcf-in-breast-cancer
#15
Sumin Oh, Chaeun Oh, Kyung Hyun Yoo
CTCF, Zn-finger protein, has been identified as multifunctional transcription factor to regulate gene expression through recruitment of other co-activators and binding to promoter regions of target genes. Furthermore, it has been proposed as an insulator protein that contributes to the establishment of functional three-dimensional chromatin structures. It could disrupt transcription through block the connection between enhancer and promoter. Previous studies revealed that various diseases including breast cancer were developed from aberrant expression of CTCF itself or their target genes...
June 26, 2017: BMB Reports
https://www.readbyqxmd.com/read/28648146/emerging-roles-of-protein-disulfide-isomerase-in-cancer
#16
Eunyoug Lee, Do Hee Lee
Protein disulfide isomerase (PDI) family is a group of multifunctional endoplasmic reticulum (ER) enzymes mediating the formation of disulfide bonds, catalyzing the cysteine-based redox reactions and assisting the quality control of the client proteins. Recent structural and functional studies have demonstrated that PDI members not only play an essential role in the proteostasis in the ER but also exert diverse effects in numerous human diseases including cancer and neurodegenerative diseases. Increasing evidence suggests that PDI is actively involved in the proliferation, survival, and metastasis of several types of cancer cells...
June 26, 2017: BMB Reports
https://www.readbyqxmd.com/read/28648145/er-membrane-protein-complex-subunit-6-emc6-is-a-novel-tumor-suppressor-in-gastric-cancer
#17
Xiaokun Wang, Yan Xia, Chentong Xu, Xin Lin, Peng Xue, Shijie Zhu, Yun Bai, Yingyu Chen
Endoplasmic reticulum (ER) membrane protein complex subunit 6 (EMC6) is a novel human autophagy-related molecule. Here, using tissue microarray and immunohistochemistry, we report that EMC6 protein is lost or reduced in glandular cells of patients with gastric adenocarcinoma, compared to normal stomach mucosa. Overexpression of EMC6 in gastric cancer cells inhibited cell growth, migration, and invasion, and induced apoptosis and cell cycle arrest at S-phase. Further investigation suggested that EMC6 overexpression in BGC823 cells reduced tumorigenicity in a xenograft model, demonstrating that EMC6 has the characteristics of a tumor suppressor...
June 26, 2017: BMB Reports
https://www.readbyqxmd.com/read/28648144/repression-of-the-f-box-protein-skp2-is-essential-for-actin-damage-induced-tetraploid-g1-arrest
#18
Yongsam Jo, Deug Y Shin
We previously reported that p53 plays as a key regulator in tetraploid G1 checkpoint, which is activated by actin damage-induced cytokinesis blockade and then prevents uncoupled DNA replication and nuclear division without cytokinesis. In this study, we investigated a role of Skp2, which targets CDK2 inhibitor p27/Kip1, in actin damage-induced tetraploid G1 arrest. Expression of Skp2 was decreased, but p27/Kip1 was increased after actin damage-induced cytokinesis blockade. The roles of Skp2 repression in tetraploid G1 arrest was investigated by analyzing the effects of ectopic expression of Skp2...
June 26, 2017: BMB Reports
https://www.readbyqxmd.com/read/28602162/endothelial-mir-26a-regulates-vegf-nogo-b-receptor-mediated-angiogenesis
#19
Ha-Neul Jo, Hyesoo Kang, Aram Lee, Jihea Choi, Woochul Chang, Myeong-Sok Lee, Jongmin Kim
The Nogo-B receptor (NgBR) is necessary for not only Nogo-B-mediated angiogenesis but also vascular endothelial growth factor (VEGF)-induced angiogenesis. However, the molecular mechanisms underlying the regulatory role of the VEGF-NgBR axis in angiogenesis are not fully understood. Here, we report that miR-26a serves as a critical regulator of VEGF-mediated angiogenesis through directly targeting NgBR in endothelial cells (ECs). Stimulation of ECs by VEGF increased the expression of NgBR and decreased the expression of miR-26a...
June 12, 2017: BMB Reports
https://www.readbyqxmd.com/read/28602161/cytoprotective-effect-exerted-by-geraniin-in-hepg2-cells-is-through-microrna-mediated-regulation-of-bach-1-and-ho-1
#20
Hoda Aayadi, Smriti P K Mittal, Anjali Deshpande, Makarand Gore, Saroj S Ghaskadbi
Geraniin, a hydrolysable tannin, used in traditional medicine in Southeast Asia, is known to exhibit various biological activities. As an antioxidant it is known to up-regulate phase II enzyme Heme oxygenase-1 (HO-1). However its mechanism is not clearly understood. Nuclear factor erythroid-derived 2 related factor 2 (Nrf-2) is transcriptionally up-regulated by Extracellular signal-regulated kinase (ERK) 1/2 and retained in nucleus due to inactivated Glycogen synthase kinase 3 beta (GSK-3β). Geraniin additionally down-regulates expression of microRNA 217 and 377 (miR-217 and miR-377) which target HO-1 mRNA...
June 12, 2017: BMB Reports
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