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two newly identified factors that restrict diverse viruses, dXPO1 and dRUVBL1 contributed to antiviral defense at the organismal level in adult flies
Nuclear export of TIS11 proteins is mediated by CRM1 through diverging nuclear export signals, while their nuclear import mechanism may rely on a highly conserved signal whose activity is negatively regulated by ZnF2 folding.
HPO promotes the translocation of SD to the cytoplasm in a CRM1-dependent manner
Exportin-1 is a nuclear export receptor for expanded polyQ containing proteins.
Nuclear localization of the ecdysteroid receptor (EcR) is increased in HeLa cells if exportin-1 (CRM1) is knocked down by siRNA against exportin.
Data show that downregulation of YAN involves CRM1-mediated nuclear export, and that MAE is involved in MAPK phosphorylationof YAN.
A major function of DNup88 is to anchor DNup214 and CRM1 on the nuclear envelope and thereby attenuate NES-mediated nuclear export.
Phosphorylation of Yan favors Crm1 in this competition and counteracts inhibition of nuclear export by Mae
two functional nuclear export signals are in the Sima basic helix-loop-helix (bHLH) domain and promote CRM1-dependent nuclear export
We describe three in vitro reconstituted disassembly intermediates, which show binding of a Crm1 export complex via two FG-repeat patches, cargo-release by RanBP2's Ran-binding domains and retention of free Crm1 at RanBP2 after Ran-GTP hydrolysis.
Nuclear entrapment of p33ING1b by inhibition of exportin-1 triggers apoptosis in head and neck squamous cell cancer cells.
CDK4 and XPO1 are not altered in a rare undifferentiated sarcoma, making them therapeutic targets
The subcellular distributions of IkappaB and NFkappaB are indicative of carcinogenesis. Inhibition of XPO1 results in intranuclear retention of IkappaB, which inhibits NFkappaB and thereby provides a novel mechanism for drug therapy in sarcoma. This effect can be further enhanced in relatively selinexor-resistant sarcoma cell lines by pretreatment with the proteasome inhibitor carfilzomib.
this work advocates for assessing 2p+ and XPO1 mutations before choosing a chronic lymphocytic leukemia therapy.
Importin-beta and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function.
We provide evidence for a regulatory role of CRM1 (chromosome-region-maintenance-1; also known as XPO1, exportin-1) in juxta-nuclear microtubule-dependent adenovirus transport. Leptomycin B (LMB) abolishes nuclear targeting of adenovirus. It binds to CRM1, precludes CRM1-cargo binding and blocks signal-dependent nuclear export.
in leukemia cell lines an XPO1 heterozygous mutation confers similar resistance against selinexor as homozygous substitution, demonstrating that SINE resistance can be obtained by a single and dominant mutation of the cysteine528 residue in XPO1
XPO1 inhibitor combination therapy with bortezomib or carfilzomib induces nuclear localization of IkappaBalpha and overcomes acquired proteasome inhibitor resistance in human multiple myeloma.
KPT-8602 is highly specific for XPO1 inhibition and demonstrates potent anti-leukemic activity supporting clinical application of the second-generation SINE compound for the treatment of Acute Lymphoblastic Leukemia
Taken together, these results provide evidence that XPO1 inhibition represents a new therapeutic strategy for overcoming platinum resistance in women with ovarian cancer
Selinexor, a selective inhibitor of XPO1, is currently being tested as single agent in clinical trials in acute myeloid leukemia.
Nuclear export receptor CRM1 recognizes diverse conformations in nuclear export signals.
These results suggest a differential interaction between human Crm1 and mouse Crm1 and many lentiviral Rev proteins, which may partially explain the HIV replicative defect in mice.
Combined targeting of XPO1 and ERalpha in several tamoxifen-resistant cell lines and tumor xenografts with the XPO1 inhibitor, Selinexor, and tamoxifen restored tamoxifen sensitivity and prevented recurrence in vivo.
Results suggest that the cancer-inhibitory activity of sodium butyrate and its derivatives on liver carcinogenesis may be attributed to retention of p53 and CRM1 proteins in the nucleus, an event that may trigger activation of p53-mediated apoptotic cell death in neoplastic cells.
REVIEW: the role of XPO1 in B cell hematological malignancies
Selinexor, an inhibitor of XPO1, induces cell cycle arrest independent of alterations in the KIT signaling pathway.
Authors investigated the clinical significance of XPO1 mutations in patients with CLL.
Here, the authors identify cellular nuclear transport factor 2 (NTF2)-like export protein 1 (NXT1) as a novel binding partner of nucleoprotein (NP) that stimulates NP-mediated nuclear export via the CRM1-dependent pathway.
CRM1 binds to Axin in the presence of RanGTP
Data show that administration of a single dose of selinexor bound Exportin 1 (XPO1/CRM1) for minimally 72 hours both in vitro and in vivo.
These results suggest a model wherein HIV-1 Rev-associated nuclear export signals cooperate to regulate the number or quality of CRM1's interactions with viral Rev/RRE ribonucleoprotein complexes in the nucleus.
map the nuclear import and export signals of Dp71d by truncation and point mutant analysis, showing for the first time Dp71d shuttles between nucleus and cytoplasm mediated by conventional nuclear transporters, importin (IMP) alpha/beta and the exportin CRM1
AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1.
A CRM1-mediated nuclear export signal is essential for cytoplasmic localization of neurogenin 3 in neurons.
Bioavailable CRM1 inhibitor KPT-251 significantly inhibited renal cell carcinoma growth in vivo with the expected on target effects and no obvious toxicity.
CRM1 augments production of infectious human and feline immunodeficiency viruses from murine cells
CaMKI vies with CRM1/exportin 1 for access to a nuclear export signal, and assembly of a CaMKI-14-3-3 zeta-CCTalpha complex is a key effector mechanism that drives nuclear CCTalpha translocation.
Transcription-independent role of Bach1 in mitosis through a nuclear exporter Crm1-dependent mechanism.
CRM1 protein-mediated regulation of nuclear clusterin (nCLU), an ionizing radiation-stimulated, Bax-dependent pro-death factor
UAP56 and URH49 exhibit an intrinsic CRM1-independent nucleocytoplasmic shuttling
p53 subcellular localization resulting from CRM1 alterations may play an important role in lung tumorigenesis
These results clearly demonstrate that Nup98 functions as a novel shuttling cofactor for Crm1-mediated nuclear export in conjunction with RanBP3.
Crm1 inhibition promotes accumulation of p65 NF-kB in nuclei of poly(ADP-ribose) polymerase-1-deficient cells and reverses expression of NF-kappaB-dependent genes upon Toll-like receptor (TLR)4 stimulation.
results indicate that the minute virus of mice (MVMi) NS2-CRM1 interaction is an important determinant of MVMi virulence that can be modulated in nature
C-terminal sequences direct cyclin D1-CRM1 binding
NPM/B23 localizes between the paired centrioles of unduplicated centrosomes; inhibition of Crm1 nuclear export receptor results in both accumulation of cyclin E at centrosomes and efficient dissociation of NPM/B23 from centrosomes
Induction of differentiation in epidermal keratinocytes activates a specific program for post-transcriptional downregulation of E2F1, which involves signaling through p38 and activation of CRM1-dependent nuclear export
These results strongly suggest that CRM1 mediated-nuclear export of HDAC7 is independent of HDAC7 phosphorylation and its association with 14-3-3s.
The protein encoded by this gene mediates leucine-rich nuclear export signal (NES)-dependent protein transport. Exportin 1 specifically inhibits the nuclear export of Rev and U snRNAs. It is involved in the control of several cellular processes by controlling the localization of cyclin B, MPAK, and MAPKAP kinase 2. This protein also regulates NFAT and AP-1.
, chromosomal region maintenance 1
, exportin 1
, exportin 1 (CRM1 homolog, yeast)
, exportin 1-like
, CRM1, yeast, homolog
, chromosome region maintenance 1 protein homolog
, exportin 1 (CRM1, yeast, homolog)
, exportin-1 (required for chromosome region maintenance)
, nuclear export factor CRM1
, CRM1/XPO1 protein