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https://www.readbyqxmd.com/read/28712389/rescuing-p53-from-mdm2-by-intrinsically-unfolded-sumo-protease-4
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28602160/kahweol-inhibits-lipid-accumulation-and-induces-glucose-uptake-through-activation-of-amp-activated-protein-kinase-ampk
#14
Jung-Hwan Baek, Nam-Jun Kim, Jun-Kyu Song, Kyung-Hee Chun
Weight loss ≥5% is sufficient to significantly reduce health risks for people with obesity; therefore, development of novel weight loss compounds with reduced toxicity is urgently required. After screening of natural compounds with anti-adipogenesis properties in 3T3-L1 cells, we determined that kahweol, a coffee-specific diterpene, inhibited adipogenesis. Kahweol reduced lipid accumulation and expression levels of adipogenesis and lipid accumulation-related factors. Levels of Phosphorylated AKT and phosphorylated JAK2, which induce lipid accumulation, decreased in kahweol-treated cells...
June 12, 2017: BMB Reports
https://www.readbyqxmd.com/read/28571594/dual-torcs-driven-and-b56-orchestrated-signaling-network-guides-eukaryotic-cell-migration
#15
Lou W Kim
Different types of eukaryotic cells may adopt seemingly distinct modes of directional cell migration. However, several core aspects are regarded common whether the movement is either ameoboidal or mesenchymal. The region of cells facing the attractive signal is often termed leading edge where lamellipodial structures dominates and the other end of the cell called rear end is often mediating cytoskeletal F-actin contraction involving Myosin-II. Dynamic remodeling of cell-to-matrix adhesion involving integrin is also evident in many types of migrating cells...
June 2, 2017: BMB Reports
https://www.readbyqxmd.com/read/28571593/structure-signaling-and-the-drug-discovery-of-the-ras-oncogene-protein
#16
Chang Woo Han, Mi Suk Jeong, Se Bok Jang
Mutations in Ras GTPase are among the most common genetic alterations in human cancers. Despite extensive research investigating Ras proteins, their functions still remain a challenge over a long period of time. The currently available data suggests that solving the outstanding issues regarding Ras could lead to development of effective drugs that could have a significant impact on cancer treatment. Developing a better understanding of their biochemical properties or modes of action, along with improvements in their pharmacologic profiles, clinical design and scheduling will enable the development of more effective therapies...
June 2, 2017: BMB Reports
https://www.readbyqxmd.com/read/28539160/phosphorylation-of-p53-at-threonine-155-is-required-for-jab1-mediated-nuclear-export-of-p53
#17
Eun-Woo Lee, Wonkyung Oh, Hosung Paul Song, Won Kon Kim
The Jun activation-domain binding protein 1 (Jab1) induces p53 nuclear export and cytoplasmic degradation. However, the underlying mechanism is not clearly addressed. Here, we identify that phosphorylation at threonine 155 residue is indispensable for Jab1-mediated p53 nuclear export. Jab1 stimulated phosphorylation of p53 at T155, which was inhibited by curcumin, an inhibitor of COP9 signalosome (CSN)-associated kinases. T155E mutant, which mimics phosphorylated p53, exhibited spontaneous cytoplasmic localization in the absence of Jab1...
May 25, 2017: BMB Reports
https://www.readbyqxmd.com/read/28539159/anti-microbial-peptide-sr-0379-stimulates-human-endothelial-progenitor-cell-mediated-repair-of-peripheral-artery-diseases
#18
Tae Wook Lee, Soon Chul Heo, Yang Woo Kwon, Gyu Tae Park, Jung Won Yoon, Seung-Chul Kim, Il Ho Jang, Jae Ho Kim
Ischemia is a major plague of modern life. In the search of peptide drug candidates for curing ischemic disease, we evaluated the effects of an anti-microbial peptide SR-0379 on stem cell-mediated therapy of ischemic diseases. Migration and tube-forming ability of human endothelial progenitor cells (EPCs) were enhanced by SR-0379 treatment in vitro. Intramuscular administration of SR-0379 into murine ischemic hindlimb significantly enhanced blood perfusion and decreased tissue necrosis, and increased the number of blood vessels in ischemic muscle...
May 25, 2017: BMB Reports
https://www.readbyqxmd.com/read/28454607/a-fca-mediated-epigenetic-route-towards-thermal-adaptation-of-autotrophic-development-in-plants
#19
Hyo-Jun Lee, Jun-Ho Ha, Chung-Mo Park
Plants are able to recognize even small changes of surrounding temperatures to optimize their growth and development. At warm temperatures, plants exhibit diverse architectural adjustments, including hypocotyl and petiole elongation, leaf hyponasty, and reduced stomatal density. However, it was unknown until recently how warm temperatures affect the early stages of seedling development. In our recent study, we demonstrated that the RNA-binding protein FCA is critical for sustaining chlorophyll biosynthesis during early seedling development, which is a prerequisite for autotrophic transition, at warm temperatures...
April 29, 2017: BMB Reports
https://www.readbyqxmd.com/read/28454606/therapeutic-implication-of-autophagy-in-neurodegenerative-diseases
#20
Md Ataur Rahman, Hyewhon Rhim
Autophagy, a catabolic process to maintain intracellular homeostasis, has been recently focus in numerous human disease conditions, such as aging, cancer, development, immunity, longevity, and neurodegeneration. However, sustaining autophagy is essential for cell survival and dysregulate autophagy is anticipated to speed up neurodegeneration progression; although, the actual molecular mechanism is not yet fully understood. In contrast, emerging evidence suggests that basal autophagy is necessary for removal of misfolded aggregation proteins and damaged cellular organelles through lysosomal mediated degradation...
April 29, 2017: BMB Reports
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