keyword
MENU ▼
Read by QxMD icon Read
search

Crm1

keyword
https://www.readbyqxmd.com/read/29137251/exportin-1-xpo1-inhibition-leads-to-restoration-of-tumor-suppressor-mir-145-and-consequent-suppression-of-pancreatic-cancer-cell-proliferation-and-migration
#1
Asfar S Azmi, Yiwei Li, Irfana Muqbil, Amro Aboukameel, William Senapedis, Erkan Baloglu, Yosef Landesman, Sharon Shacham, Michael G Kauffman, Philip A Philip, Ramzi M Mohammad
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer related deaths in the United States with a majority of these patients dying from aggressively invasive and metastatic disease. There is growing evidence that suggests an important role for microRNAs (miRNAs) in the pathobiology of aggressive PDAC. In this study, we found that the expression of miR-145 was significantly lower in PDAC cells when compared to normal pancreatic duct epithelial cells. Here we show that inhibition of the nuclear exporter protein exportin 1 (XPO1; also known as chromosome maintenance region 1 [CRM1]) by siRNA knockdown or by the Selective Inhibitor of Nuclear Export (SINE) compound (KPT-330; selinexor) increases miR-145 expression in PDAC cells resulting in the decreased cell proliferation and migration capacities...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29101390/l290p-v-mutations-increase-erk3-s-cytoplasmic-localization-and-migration-invasion-promoting-capability-in-cancer-cells
#2
Hadel Alsaran, Lobna Elkhadragy, Astha Shakya, Weiwen Long
Protein kinases are frequently mutated in human cancers, which leads to altered signaling pathways and contributes to tumor growth and progression. ERK3 is an atypical mitogen-activated protein kinase (MAPK) containing an S-E-G activation motif rather than the conserved T-X-Y motif in conventional MAPKs such as ERK1/2. Recent studies have revealed important roles for ERK3 in cancers. ERK3 promotes cancer cell migration/invasion and tumor metastasis, and its expression is upregulated in multiple cancers. Little is known, however, regarding ERK3 mutations in cancers...
November 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29053568/mutation-of-a-conserved-nuclear-export-sequence-in-chikungunya-virus-capsid-protein-disrupts-host-cell-nuclear-import
#3
Susan C Jacobs, Adam Taylor, Lara J Herrero, Suresh Mahalingam, John K Fazakerley
Transmitted by mosquitoes; chikungunya virus (CHIKV) is responsible for frequent outbreaks of arthritic disease in humans. CHIKV is an arthritogenic alphavirus of the Togaviridae family. Capsid protein, a structural protein encoded by the CHIKV RNA genome, is able to translocate to the host cell nucleus. In encephalitic alphaviruses nuclear translocation induces host cell shut off; however, the role of capsid protein nuclear localisation in arthritogenic alphaviruses remains unclear. Using replicon systems, we investigated a nuclear export sequence (NES) in the N-terminal region of capsid protein; analogous to that found in encephalitic alphavirus capsid but uncharacterised in CHIKV...
October 20, 2017: Viruses
https://www.readbyqxmd.com/read/29028476/differential-interaction-between-human-and-murine-crm1-and-lentiviral-rev-proteins
#4
Yan Yue, Ayse K Coskun, Navneet Jawanda, Jim Auer, Richard E Sutton
Mice have multiple obstacles to HIV replication, including a block of unspliced and partially spliced viral mRNA nuclear export. In human, Rev binds to the Rev-response element and human (h) Crm1, facilitating nuclear export of RRE-containing viral RNAs. Murine (m) Crm1 is less functional than hCrm1 in this regard. Here we demonstrated that in biochemical experiments mCrm1 failed to interact with HIV Rev whereas hCrm1 did. In genetic experiments in human cells, we observed a modest but significant differential effect between mCrm1 and hCrm1, which was also true of other lentiviral Revs tested...
October 10, 2017: Virology
https://www.readbyqxmd.com/read/28992066/tfiia-transcriptional-activity-is-controlled-by-a-cleave-and-run-exportin-1-taspase-1-switch
#5
Christian Schrenk, Verena Fetz, Cecilia Vallet, Christina Heiselmayer, Elisabeth Schröder, Astrid Hensel, Angelina Hahlbrock, Désirée Wünsch, Dorothee Goesswein, Carolin Bier, Negusse Habtemichael, Günter Schneider, Roland H Stauber, Shirley K Knauer
Transcription factor TFIIA is controlled by complex regulatory networks including proteolysis by the protease Taspase 1, though the full impact of cleavage remains elusive. Here, we demonstrate that in contrast to the general assumption, de novo produced TFIIA is rapidly confined to the cytoplasm via an evolutionary conserved nuclear export signal (NES, amino acids 21VINDVRDIFL30), interacting with the nuclear export receptor Exportin-1/chromosomal region maintenance 1 (Crm1). Chemical export inhibition or genetic inactivation of the NES not only promotes TFIIA's nuclear localization but also affects its transcriptional activity...
August 10, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28981101/reciprocal-amplification-of-caspase-3-activity-by-nuclear-export-of-a-putative-human-rna-modifying-protein-pus10-during-trail-induced-apoptosis
#6
Sujata Jana, Andrew C Hsieh, Ramesh Gupta
Pus10 is a pseudouridine synthase present in Archaea and Eukarya, but not in Bacteria and yeast. It has been suggested that the human PUS10 (DOBI) gene is needed during TRAIL-induced apoptosis. We analyzed the role of PUS10 in TRAIL-induced apoptosis by immunofluorescence, immunoblotting and several indicators of apoptosis. We examined several TRAIL-sensitive cell lines and we also examined some resistant cell lines after treatment with cycloheximide. PUS10 is mainly present in the nucleus. Early during apoptosis, PUS10 translocates to mitochondria via CRM1-mediated export with the concurrent release of cytochrome c and SMAC...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28974580/sumoylation-regulates-nuclear-accumulation-and-signaling-activity-of-the-soluble-intracellular-domain-of-the-erbb4-receptor-tyrosine-kinase
#7
Anna Maria Knittle, Maria Helkkula, Mark S Johnson, Maria Sundvall, Klaus Elenius
Erb-B2 receptor tyrosine kinase 4 (ErbB4) is a kinase that can signal via a proteolytically released intracellular domain (ICD) in addition to classical receptor tyrosine kinase-activated signaling cascades. Previously, we have demonstrated that ErbB4 ICD is posttranslationally modified by the small ubiquitin-like modifier (SUMO) and functionally interacts with the PIAS3 SUMO E3 ligase. However, direct evidence of SUMO modification in ErbB4 signaling has remained elusive. Here, we report that the conserved lysine residue 714 in the ErbB4 ICD undergoes SUMO modification, which was reversed by sentrin-specific proteases (SENPs) 1, 2 and 5...
October 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28961161/venezuelan-equine-encephalitis-virus-capsid-the-clever-caper
#8
REVIEW
Lindsay Lundberg, Brian Carey, Kylene Kehn-Hall
Venezuelan equine encephalitis virus (VEEV) is a New World alphavirus that is vectored by mosquitos and cycled in rodents. It can cause disease in equines and humans characterized by a febrile illness that may progress into encephalitis. Like the capsid protein of other viruses, VEEV capsid is an abundant structural protein that binds to the viral RNA and interacts with the membrane-bound glycoproteins. It also has protease activity, allowing cleavage of itself from the growing structural polypeptide during translation...
September 29, 2017: Viruses
https://www.readbyqxmd.com/read/28942004/leptomycin-b-reduces-primary-and-acquired-resistance-of-gefitinib-in-lung-cancer-cells
#9
Zhongwei Liu, Weimin Gao
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib has demonstrated dramatic clinical efficacy in non-small cell lung cancer (NSCLC) patients. However, its therapeutic efficacy is ultimately limited by the development of acquired drug resistance. The aim of this study was to explore the potential utility of chromosome region maintenance 1 (CRM1) inhibitor leptomycin B (LMB) in combination with gefitinib to overcome primary and acquired gefitinib resistance in NSCLC cells. The combinative effects of gefitinib and LMB were evaluated by MTT and its underlining mechanism was assessed by flow cytometry and Western blot...
November 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28830558/identification-of-a-homogenous-structural-basis-for-oligomerization-by-retroviral-rev-like-proteins
#10
Chijioke N Umunnakwe, Karin S Dorman, Drena Dobbs, Susan Carpenter
BACKGROUND: Rev-like proteins are post-transcriptional regulatory proteins found in several retrovirus genera, including lentiviruses, betaretroviruses, and deltaretroviruses. These essential proteins mediate the nuclear export of incompletely spliced viral RNA, and act by tethering viral pre-mRNA to the host CRM1 nuclear export machinery. Although all Rev-like proteins are functionally homologous, they share less than 30% sequence identity. In the present study, we computationally assessed the extent of structural homology among retroviral Rev-like proteins within a phylogenetic framework...
August 22, 2017: Retrovirology
https://www.readbyqxmd.com/read/28791779/crystal-structure-of-the-xpo1p-nuclear-export-complex-bound-to-the-sxfg-pxfg-repeats-of-the-nucleoporin-nup42p
#11
Masako Koyama, Hidemi Hirano, Natsuki Shirai, Yoshiyuki Matsuura
Xpo1p (yeast CRM1) is the major nuclear export receptor that carries a plethora of proteins and ribonucleoproteins from the nucleus to cytoplasm. The passage of the Xpo1p nuclear export complex through nuclear pore complexes (NPCs) is facilitated by interactions with nucleoporins (Nups) containing extensive repeats of phenylalanine-glycine (so-called FG repeats), although the precise role of each Nup in the nuclear export reaction remains incompletely understood. Here we report structural and biochemical characterization of the interactions between the Xpo1p nuclear export complex and the FG repeats of Nup42p, a nucleoporin localized at the cytoplasmic face of yeast NPCs and has characteristic SxFG/PxFG sequence repeat motif...
August 8, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28761359/nuclear-ddx3-expression-predicts-poor-outcome-in-colorectal-and-breast-cancer
#12
Marise R Heerma van Voss, Farhad Vesuna, Guus M Bol, Jan Meeldijk, Ana Raman, G Johan Offerhaus, Horst Buerger, Arvind H Patel, Elsken van der Wall, Paul J van Diest, Venu Raman
PURPOSE: DEAD box protein 3 (DDX3) is an RNA helicase with oncogenic properties that shuttles between the cytoplasm and nucleus. The majority of DDX3 is found in the cytoplasm, but a subset of tumors has distinct nuclear DDX3 localization of yet unknown biological significance. This study aimed to evaluate the significance of and mechanisms behind nuclear DDX3 expression in colorectal and breast cancer. METHODS: Expression of nuclear DDX3 and the nuclear exporter chromosome region maintenance 1 (CRM1) was evaluated by immunohistochemistry in 304 colorectal and 292 breast cancer patient samples...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28760339/crystal-structure-of-importin-%C3%AE-3-bound-to-the-nuclear-localization-signal-of-ran-binding-protein-3
#13
Masako Koyama, Yoshiyuki Matsuura
Ran-binding protein 3 (RanBP3) is a primarily nuclear Ran-binding protein that functions as an accessory factor in the Ran GTPase system. RanBP3 associates with Ran-specific nucleotide exchange factor RCC1 and enhances its catalytic activity towards Ran. RanBP3 also promotes CRM1-mediated nuclear export as well as CRM1-independent nuclear export of β-catenin, Smad2, and Smad3. Nuclear import of RanBP3 is dependent on the nuclear import adaptor protein importin-α and, RanBP3 is imported more efficiently by importin-α3 than by other members of the importin-α family...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28753564/exportin-1-xpo1-inhibition-leads-to-restoration-of-tumor-suppressor-mir-145-and-consequent-suppression-of-pancreatic-cancer-cell-proliferation-and-migration
#14
Asfar S Azmi, Yiwei Li, Irfana Muqbil, Amro Aboukameel, William Senapedis, Erkan Baloglu, Yosef Landesman, Sharon Shacham, Michael G Kauffman, Philip A Philip, Ramzi M Mohammad
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer related deaths in the United States with a majority of these patients dying from aggressively invasive and metastatic disease. There is growing evidence that suggests an important role for microRNAs (miRNAs) in the pathobiology of aggressive PDAC. In this study, we found that the expression of miR-145 was significantly lower in PDAC cells when compared to normal pancreatic duct epithelial cells. Here we show that inhibition of the nuclear exporter protein exportin 1 (XPO1; also known as chromosome maintenance region 1 [CRM1]) by siRNA knockdown or by the Selective Inhibitor of Nuclear Export (SINE) compound (KPT-330; selinexor) increases miR-145 expression in PDAC cells resulting in the decreased cell proliferation and migration capacities...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28702009/crm1-inhibitors-for-antiviral-therapy
#15
REVIEW
Cynthia Mathew, Reena Ghildyal
Infectious diseases are a major global concern and despite major advancements in medical research, still cause significant morbidity and mortality. Progress in antiviral therapy is particularly hindered by appearance of mutants capable of overcoming the effects of drugs targeting viral components. Alternatively, development of drugs targeting host proteins essential for completion of viral lifecycle holds potential as a viable strategy for antiviral therapy. Nucleocytoplasmic trafficking pathways in particular are involved in several pathological conditions including cancer and viral infections, where hijacking or alteration of function of key transporter proteins, such as Chromosome Region Maintenance1 (CRM1) is observed...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28689976/crm1-inhibitory-and-antiproliferative-activities-of-novel-4-alkyl-substituted-klavuzon-derivatives
#16
Tuğçe Kanbur, Murat Kara, Meltem Kutluer, Ayhan Şen, Murat Delman, Aylin Alkan, Hasan Ozan Otaş, İsmail Akçok, Ali Çağır
Klavuzons are 6-(naphthalen-1-yl) substituted 5,6-dihydro-2H-pyran-2-one derivatives showing promising antiproliferative activities in variety of cancer cell lines. In this work, racemic syntheses of nine novel 4'-alkyl substituted klavuzon derivatives were completed in eight steps and anticancer properties of these compounds were evaluated. It is found that size of the substituent has dramatic effect over the potency and selectivity of the cytotoxic activity in cancerous and healthy pancreatic cell lines. The size of the substituent can also effect the CRM1 inhibitory properties of klavuzon derivatives...
August 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28600321/importin-beta-and-crm1-control-a-ranbp2-spatiotemporal-switch-essential-for-mitotic-kinetochore-function
#17
Eugenia Gilistro, Valeria de Turris, Michela Damizia, Annalisa Verrico, Sara Moroni, Riccardo De Santis, Alessandro Rosa, Patrizia Lavia
Protein conjugation with SUMO is a post-translational modification that modulates protein interactions and localisation. RANBP2 is a large nucleoporin endowed with SUMO E3 ligase and SUMO-stabilising activity and is implicated in some cancer types. RANBP2 is part of a larger complex, comprising SUMO-modified RANGAP1, the GTP-hydrolysis activating factor for the GTPase RAN. During mitosis, the RANBP2/SUMO-RANGAP1 complex localises to the mitotic spindle and to kinetochores after microtubule attachment. Here we have addressed the mechanisms that regulate this localisation and how they affect kinetochore functions...
June 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28582471/sumo-regulates-p21cip1-intracellular-distribution-and-with-p21cip1-facilitates-multiprotein-complex-formation-in-the-nucleolus-upon-dna-damage
#18
Sonia Brun, Neus Abella, Maria T Berciano, Olga Tapia, Montserrat Jaumot, Raimundo Freire, Miguel Lafarga, Neus Agell
We previously showed that p21Cip1 transits through the nucleolus on its way from the nucleus to the cytoplasm and that DNA damage inhibits this transit and induces the formation of p21Cip1-containing intranucleolar bodies (INoBs). Here, we demonstrate that these INoBs also contain SUMO-1 and UBC9, the E2 SUMO-conjugating enzyme. Furthermore, whereas wild type SUMO-1 localized in INoBs, a SUMO-1 mutant, which is unable to conjugate with proteins, does not, suggesting the presence of SUMOylated proteins at INoBs...
2017: PloS One
https://www.readbyqxmd.com/read/28515232/the-nuclear-export-factor-crm1-controls-juxta-nuclear-microtubule-dependent-virus-transport
#19
I-Hsuan Wang, Christoph J Burckhardt, Artur Yakimovich, Matthias K Morf, Urs F Greber
Transport of large cargo through the cytoplasm requires motor proteins and polarized filaments. Viruses that replicate in the nucleus of post-mitotic cells use microtubules and the dynein-dynactin motor to traffic to the nuclear membrane and deliver their genome through nuclear pore complexes (NPCs) into the nucleus. How virus particles (virions) or cellular cargo are transferred from microtubules to the NPC is unknown. Here, we analyzed trafficking of incoming cytoplasmic adenoviruses by single-particle tracking and super-resolution microscopy...
July 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28490361/adducin-family-proteins-possess-different-nuclear-export-potentials
#20
Chia-Mei Liu, Wen-Hsin Hsu, Wan-Yi Lin, Hong-Chen Chen
BACKGROUND: The adducin (ADD) family proteins, namely ADD1, ADD2, and ADD3, are actin-binding proteins that play important roles in the stabilization of membrane cytoskeleton and cell-cell junctions. All the ADD proteins contain a highly conserved bipartite nuclear localization signal (NLS) at the carboxyl termini, but only ADD1 can localize to the nucleus. The reason for this discrepancy is not clear. METHODS: To avoid the potential effect of cell-cell junctions on the distribution of ADD proteins, HA epitope-tagged ADD proteins and mutants were transiently expressed in NIH3T3 fibroblasts and their distribution in the cytoplasm and nucleus was examined by immunofluorescence staining...
May 10, 2017: Journal of Biomedical Science
keyword
keyword
85288
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"