18,600 results match your criteria nuclear export


SARS-CoV-2 uses a multipronged strategy to impede host protein synthesis.

Nature 2021 May 12. Epub 2021 May 12.

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 19 pandemic. Coronaviruses developed varied mechanisms to repress host mRNA translation to allow the translation of viral mRNAs and concomitantly block the cellular innate immune response. Although different SARS-CoV-2 proteins are implicated in host expression shutoff, a comprehensive picture of the effects of SARS-CoV-2 infection on cellular gene expression is lacking. Read More

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A high-throughput genome-wide RNAi screen identifies modifiers of survival motor neuron protein.

Cell Rep 2021 May;35(6):109125

Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, Bethesda, MD 20814, USA. Electronic address:

Spinal muscular atrophy (SMA) is a debilitating neurological disorder marked by degeneration of spinal motor neurons and muscle atrophy. SMA results from mutations in survival motor neuron 1 (SMN1), leading to deficiency of survival motor neuron (SMN) protein. Current therapies increase SMN protein and improve patient survival but have variable improvements in motor function, making it necessary to identify complementary strategies to further improve disease outcomes. Read More

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Nicotine-induced ILF2 facilitates nuclear mRNA export of pluripotency factors to promote stemness and chemoresistance in human esophageal cancer.

Cancer Res 2021 May 11. Epub 2021 May 11.

Department of Experimental Research, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center

Balancing mRNA nuclear export kinetics with its nuclear decay is critical for mRNA homeostasis control. How this equilibrium is aberrantly disrupted in esophageal cancer to acquire cancer stem cell properties remains unclear. Here we find that the RNA binding protein interleukin enhancer binding factor 2 (ILF2) is robustly upregulated by nicotine, a major chemical component of tobacco smoke, via activation of JAK2/STAT3 signaling and significantly correlates with poor prognosis in heavy-smoking esophageal cancer patients. Read More

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XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IkB.

Transl Oncol 2021 May 8;14(8):101114. Epub 2021 May 8.

Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue Ullmann 813 Bronx, NY 10461, United States; Department of Pediatrics, Albert Einstein College of Medicine, United States.

Across many cancer types in adults, upregulation of the nuclear-to-cytoplasmic transport protein Exportin-1 (XPO1) correlates with poor outcome and responsiveness to selinexor, an FDA-approved XPO1 inhibitor. Similar data are emerging in childhood cancers, for which selinexor is being evaluated in early phase clinical studies. Using proteomic profiling of primary tumor material from patients with high-risk neuroblastoma, as well as gene expression profiling from independent cohorts, we have demonstrated that XPO1 overexpression correlates with poor patient prognosis. Read More

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Structure-Guided Design of the First Noncovalent Small-Molecule Inhibitor of CRM1.

J Med Chem 2021 May 11. Epub 2021 May 11.

Department of Pathology, State Key Laboratory of Biotherapy and Cancer Centre, West China Hospital, Sichuan University and Collaborative Innovation Centre of Biotherapy, Chengdu 610041, China.

Nuclear export factor chromosome region maintenance 1 (CRM1) is an attractive anticancer and antiviral drug target that spurred several research efforts to develop its inhibitor. Noncovalent CRM1 inhibitors are desirable, but none is reported to date. Here, we present the crystal structure of yeast CRM1 in complex with S109, a substructure of CBS9106 (under clinical test). Read More

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Oxidative Stress-Mediated YAP Dysregulation Contributes to the Pathogenesis of Pemphigus Vulgaris.

Front Immunol 2021 19;12:649502. Epub 2021 Apr 19.

Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, London, United Kingdom.

(PV) is a life-threatening autoimmune disease manifested with blisters in the skin and mucosa and caused by autoantibodies against adhesion protein desmoglein-3 (Dsg3) expressed in epithelial membrane linings of these tissues. Despite many studies, the pathogenesis of PV remains incompletely understood. Recently we have shown Dsg3 plays a role in regulating the yes-associated protein (YAP), a co-transcription factor and mechanical sensor, and constraining reactive oxygen species (ROS). Read More

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Viral-Host Interactome Analysis Reveals Chicken STAU2 Interacts With Non-structural Protein 1 and Promotes the Replication of H5N1 Avian Influenza Virus.

Front Immunol 2021 21;12:590679. Epub 2021 Apr 21.

State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

As a highly pathogenic influenza virus, H5N1 avian influenza virus (AIV) poses a great threat to poultry production and public health. H5N1 AIV has a small genome and, therefore, relies heavily on its host cellular machinery to replicate. To develop a comprehensive understanding of how H5N1 AIV rewires host cellular machinery during the course of infection, it is crucial to identify which host proteins and complexes come into physical contact with the viral proteins. Read More

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A kinome screen reveals that Nemo-like kinase is a key suppressor of hepatic gluconeogenesis.

Cell Metab 2021 Apr 29. Epub 2021 Apr 29.

Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital, School of Basic Medical Sciences, Wuhan University, Wuhan, China; Institute of Model Animal of Wuhan University, Wuhan, China; Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address:

Antihyperglycemic therapy is an important priority for the treatment of type 2 diabetes (T2D). Excessive hepatic glucose production (HGP) is a major cause of fasting hyperglycemia. Therefore, a better understanding of its regulation would be important to develop effective antihyperglycemic therapies. Read More

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The mammalian ecdysoneless protein interacts with RNA helicase DDX39A to regulate nuclear mRNA export.

Mol Cell Biol 2021 May 3. Epub 2021 May 3.

Departments of Genetics, Cell Biology and Anatomy,Biochemistry and Molecular Biology, Pathology & Microbiology, Department of Biostatistics, Eppley Institute for Research in Cancer and Allied Diseases; and Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, 985805 Nebraska Medical Center, Omaha, NE 68198.

The mammalian orthologue of Ecdysoneless (ECD) protein is required for embryogenesis, cell cycle progression, and mitigation of ER stress. Here, we identified key components of the mRNA export complexes as binding partners of ECD and characterized the functional interaction of ECD with key mRNA export-related DEAD BOX protein helicase DDX39A. We find that ECD is involved in RNA export through its interaction with DDX39A. Read More

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Choosing the right exit: How functional plasticity of the nuclear pore drives selective and efficient mRNA export.

Wiley Interdiscip Rev RNA 2021 May 2:e1660. Epub 2021 May 2.

Systems Biology, Institut de Recherches Cliniques de Montréal, Montréal, Canada.

The nuclear pore complex (NPC) serves as a central gate for mRNAs to transit from the nucleus to the cytoplasm. The ability for mRNAs to get exported is linked to various upstream nuclear processes including co-transcriptional RNP assembly and processing, and only export competent mRNPs are thought to get access to the NPC. While the nuclear pore is generally viewed as a monolithic structure that serves as a mediator of transport driven by transport receptors, more recent evidence suggests that the NPC might be more heterogenous than previously believed, both in its composition or in the selective treatment of cargo that seek access to the pore, providing functional plasticity to mRNA export. Read More

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High-resolution mapping of function and protein binding in an RNA nuclear enrichment sequence.

EMBO J 2021 May 3:e106357. Epub 2021 May 3.

Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.

The functions of long RNAs, including mRNAs and long noncoding RNAs (lncRNAs), critically depend on their subcellular localization. The identity of the sequences that dictate subcellular localization and their high-resolution anatomy remain largely unknown. We used a suite of massively parallel RNA assays and libraries containing thousands of sequence variants to pinpoint the functional features within the SIRLOIN element, which dictates nuclear enrichment through hnRNPK recruitment. Read More

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Suppression of Heterogeneous Nuclear Ribonucleoprotein C Inhibit Hepatocellular Carcinoma Proliferation, Migration, and Invasion Ras/MAPK Signaling Pathway.

Front Oncol 2021 16;11:659676. Epub 2021 Apr 16.

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Hepatocellular carcinoma (HCC), the most common malignant tumor, has high fatality and recurrence rates. Accumulating evidence shows that heterogeneous nuclear ribonucleoprotein C (HNRNPC), which is mainly involved in RNA splicing, export, and translation, promotes progression and metastasis of multiple tumor types; however, the effects of HNRNPC in HCC are unknown. In the present study, high levels of HNRNPC were detected in tumor tissues compared with para-tumor tissues by immunohistochemical and western blot assays. Read More

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Effect of Different Ratios of Yinchen and Gancao Decoction on ANIT-Treated Cholestatic Liver Injury in Mice and Its Potential Underlying Mechanism.

Front Pharmacol 2021 15;12:611610. Epub 2021 Apr 15.

Clinical Pharmacokinetic Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Cholestasis is a pathological state that leads to serious liver disease; however, therapeutic options remain limited. Yinchen and Gancao are often used in combination at different ratios in traditional Chinese formulae for the treatment of jaundice and cholestasis. In the present study, we investigated the effect of decoctions containing different ratios of Yinchen and Gancao (YGD) on alpha-naphthyl isothiocyanate (ANIT)-treated intrahepatic cholestasis (IC) in mice, and further explored the underlying mechanism. Read More

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Development and structural characterisation of human scFv targeting MDM2 spliced variant MDM2.

Mol Immunol 2021 Apr 27;135:191-203. Epub 2021 Apr 27.

Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800, Penang, Malaysia; Analytical Biochemistry Research Centre, Universiti Sains Malaysia, 11800, Penang, Malaysia. Electronic address:

The murine double minute 2 (MDM2) protein is a major negative regulator of the tumour suppressor protein p53. Under normal conditions, MDM2 constantly binds to p53 transactivation domain and/or ubiquinates p53 via its role as E3 ubiquitin ligase to promote p53 degradation as well as nuclear export to maintain p53 levels in cells. Meanwhile, amplification of MDM2 and appearance of MDM2 spliced variants occur in many tumours and normal tissues making it a prognostic indicator for human cancers. Read More

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Pharmacokinetics of Selinexor: The First-in-Class Selective Inhibitor of Nuclear Export.

Clin Pharmacokinet 2021 Apr 29. Epub 2021 Apr 29.

Karyopharm Therapeutics, 85 Wells Ave, Newton, MA, 02459, USA.

The functionality of many tumor suppressor proteins (TSPs) and oncoprotein transcript RNAs largely depend on their location within the cell. The exportin 1 complex (XPO1) transports many of these molecules from the nucleus into the cytoplasm, thereby inactivating TSPs and activating oncoprotein transcript RNAs. Aberrations of these molecules or XPO1 can increase this translocation process, leading to oncogenesis. Read More

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Targeted Therapies for Multiple Myeloma.

J Pers Med 2021 Apr 23;11(5). Epub 2021 Apr 23.

Monash Haematology, 246 Clayton Road, Clayton, VIC 3168, Australia.

Multiple myeloma continues to be a challenging disorder to treat despite improved therapies and the widespread use of proteasome inhibitors and immunomodulatory drugs. Although patient outcomes have improved, the disease continues to invariably relapse, and in the majority of cases, a cure remains elusive. In the last decade, there has been an explosion of novel drugs targeting cellular proteins essential for malignant plasma cell proliferation and survival. Read More

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Nucleocytoplasmic Transport: Regulatory Mechanisms and the Implications in Neurodegeneration.

Int J Mol Sci 2021 Apr 17;22(8). Epub 2021 Apr 17.

Department of Biology, University of Louisiana at Lafayette, 410 East Saint Mary Boulevard, Lafayette, LA 70503, USA.

Nucleocytoplasmic transport (NCT) across the nuclear envelope is precisely regulated in eukaryotic cells, and it plays critical roles in maintenance of cellular homeostasis. Accumulating evidence has demonstrated that dysregulations of NCT are implicated in aging and age-related neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and Huntington disease (HD). This is an emerging research field. Read More

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The sources and quality of Iranian honey.

Heliyon 2021 Apr 10;7(4):e06651. Epub 2021 Apr 10.

University of Goettingen, Department of Palynology and Climate Dynamics, Untere Karspüle 2, 37073, Goettingen, Germany.

Iran is one of the largest honey-producing countries worldwide and is considered as an important source of honey for international markets. However, since Iran is not registered for honey export to Europe, the quality of Iranian honey remains unknown to European traders. As the first step in filling this gap, we analyzed 225 honey samples using palynology, sensory, nuclear magnetic resonance (NMR) and conventional physicochemical analyses as outlined by the European Union coordinated control plan. Read More

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RGG-motif containing mRNA export factor Gbp2 acts as a translation repressor.

RNA Biol 2021 Apr 29:1-12. Epub 2021 Apr 29.

Department of Biochemistry, Indian Institute of Science, Bangalore, India.

Complex cascades of RNA-binding proteins regulate the mRNA metabolism and influence gene expression. Several distinct proteins act at different stages of mRNA life cycle. SR family proteins in yeast are implicated in mRNA processing and nuclear export. Read More

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Convergence of mammalian RQC and C-end rule proteolytic pathways via alanine tailing.

Mol Cell 2021 Mar 22. Epub 2021 Mar 22.

Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany; Department of Molecular Medicine, Scripps Research, Jupiter, FL 33458, USA. Electronic address:

Incompletely synthesized nascent chains obstructing large ribosomal subunits are targeted for degradation by ribosome-associated quality control (RQC). In bacterial RQC, RqcH marks the nascent chains with C-terminal alanine (Ala) tails that are directly recognized by proteasome-like proteases, whereas in eukaryotes, RqcH orthologs (Rqc2/NEMF [nuclear export mediator factor]) assist the Ltn1/Listerin E3 ligase in nascent chain ubiquitylation. Here, we study RQC-mediated proteolytic targeting of ribosome stalling products in mammalian cells. Read More

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The RNA helicase DDX5 promotes viral infection via regulating N6-methyladenosine levels on the DHX58 and NFκB transcripts to dampen antiviral innate immunity.

PLoS Pathog 2021 Apr 28;17(4):e1009530. Epub 2021 Apr 28.

Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agricultural and Forestry Sciences, Beijing, P. R. China.

Multi-functional DEAD-box helicase 5 (DDX5), which is important in transcriptional regulation, is hijacked by diverse viruses to facilitate viral replication. However, its regulatory effect in antiviral innate immunity remains unclear. We found that DDX5 interacts with the N6-methyladenosine (m6A) writer METTL3 to regulate methylation of mRNA through affecting the m6A writer METTL3-METTL14 heterodimer complex. Read More

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Selinexor in combination with topotecan in patients with advanced or metastatic solid tumors: Results of an open-label, single-center, multi-arm phase Ib study.

Invest New Drugs 2021 Apr 28. Epub 2021 Apr 28.

Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.

Background Selinexor, a first-in-class, oral selective inhibitor of nuclear export (SINE) compound inhibits Exportin-1(XPO1), had demonstrated synergistic activity with many chemotherapies and conferred in vivo antitumor efficacy in hematologic as well as solid tumors. Methods This open-label, single-center, multi-arm phase 1b study used a standard 3 + 3 design and a "basket type" expansion. Selinexor with intravenous topotecan was given in one of the 13 parallel arms. Read More

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O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport.

J Cell Biol 2021 Jul;220(7)

Department of Systems Biology, Blavatnik Institute, Harvard Medical School, Boston, MA.

Macromolecular transport across the nuclear envelope depends on facilitated diffusion through nuclear pore complexes (NPCs). The interior of NPCs contains a permeability barrier made of phenylalanine-glycine (FG) repeat domains that selectively facilitates the permeation of cargoes bound to nuclear transport receptors (NTRs). FG-repeat domains in NPCs are a major site of O-linked N-acetylglucosamine (O-GlcNAc) modification, but the functional role of this modification in nucleocytoplasmic transport is unclear. Read More

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Rapid decay of host basal mRNAs during SARS-CoV-2 infection perturbs host antiviral mRNA biogenesis and export.

bioRxiv 2021 Apr 19. Epub 2021 Apr 19.

A key feature of the mammalian innate immune response to viral infection is the transcriptional induction of interferon (IFN) genes, which encode for secreted proteins that prime the antiviral response and limit viral replication and dissemination. A hallmark of severe COVID-19 disease caused by SARS-CoV-2 is the low presence of IFN proteins in patient serum despite elevated levels of -encoding mRNAs, indicative of post-transcriptional inhibition of IFN protein production. Herein, we show SARS-CoV-2 infection limits type I and type III IFN biogenesis by preventing the release of mRNA from their sites of transcription and/or triggering their nuclear degradation. Read More

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The Nuclear Transport Protein Importin-5: A Promising Target in Oncology and Virology.

Authors:
Rémi Patouret

Chimia (Aarau) 2021 Apr;75(4):319-322

Faculty of Science, Department of Organic Chemistry, 30 quai Ernest Ansermet, CH-1211 Geneva 4;, Email:

Cellular homeostasis importantly relies on the correct nucleoplasmic distribution of a large number of RNA molecules and proteins, which are shuttled by specialized transport receptors. The nuclear import receptor importin-5, also called IPO5, RanBP5 or karyopherin β3, mediates the translocation of proteins to the nucleus, and thus regulates critical signaling pathways and cellular functions. The normal function of IPO5 appears to be disrupted in cancer cells due to aberrant overexpression. Read More

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Spodoptera frugiperda mRNA export factor interacts with and mediates the nuclear import of Autographa californica multiple nucleopolyhedrovirus ORF34 (Ac34).

Virus Res 2021 Jul 24;299:198438. Epub 2021 Apr 24.

State Key Lab of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.

Autographa californica multiple nucleopolyhedrovirus orf34 (ac34) is one of the unique genes of alphabaculoviruses. For successful alphabaculovirus replication, viral proteins must be transported to the nucleus. Our previous study showed that the nuclear localization of Ac34 was required for optimal production of budded virions. Read More

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Bamboo Transposon Research: Current Status and Perspectives.

Methods Mol Biol 2021 ;2250:257-270

State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou, Zhejiang, China.

Bamboo, a fast-growing non-timber forest plant with many uses, is a valuable species for green development. However, bamboo flowering is very infrequent, extending, in general, for up to 120 years. Ecologically, bamboo species are generally better adapted to various environments than other grasses. Read More

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January 2021

Inhibition of Host Gene Expression by KSHV: Sabotaging mRNA Stability and Nuclear Export.

Front Cell Infect Microbiol 2021 9;11:648055. Epub 2021 Apr 9.

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, United States.

Viruses are known for their ability to alter host gene expression. Kaposi sarcoma-associated herpesvirus has two proteins that obstruct host gene expression. KSHV SOX, encoded by the open reading frame 37 (ORF37), induces a widespread cytoplasmic mRNA degradation and a block on mRNA nuclear export. Read More

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Crystallin gene expression: Insights from studies of transcriptional bursting.

Exp Eye Res 2021 Apr 21;207:108564. Epub 2021 Apr 21.

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA; Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.

Cellular differentiation is marked by temporally and spatially regulated gene expression. The ocular lens is one of the most powerful mammalian model system since it is composed from only two cell subtypes, called lens epithelial and fiber cells. Lens epithelial cells differentiate into fiber cells through a series of spatially and temporally orchestrated processes, including massive production of crystallins, cellular elongation and the coordinated degradation of nuclei and other organelles. Read More

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Novel Mechanistic Observations and NES-Binding Groove Features Revealed by the CRM1 Inhibitors Plumbagin and Oridonin.

J Nat Prod 2021 Apr 23. Epub 2021 Apr 23.

Department of Pathology, State Key Laboratory of Biotherapy and Cancer Centre, West China Hospital, Sichuan University, and Collaborative Innovation Centre of Biotherapy, Chengdu 610041, People's Republic of China.

The protein chromosome region maintenance 1 (CRM1) is an important nuclear export factor and drug target in diseases such as cancer and viral infections. Several plant-derived CRM1 inhibitors including plumbagin and oridonin possess potent antitumor activities. However, their modes of CRM1 inhibition remain unclear. Read More

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