Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SILAC-Tp (12 importins)

ABSTRACT: Importin-beta family proteins are nucleocytoplasmic transport receptors (NTRs), and they transport most nuclear proteins as their cargoes into and out of the nuclei. Human cells have 20 species of importin-beta family NTRs, of which 10 (importin-beta, transportin-1, -2, -SR, importin-4, -5, -7, -8, -9, and -11) are nuclear import receptors and 2 (importin-13, and exportin-4) are bi-directional receptors. Here, we identified the import cargo proteins of these 12 NTRs by a method called SILAC-Tp, which employs stable isotope labeling with amino acids in cell culture (SILAC), an in vitro reconstituted transport system, and LC-MS/MS.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Naoko Imamoto

PROVIDER: MSV000080815 | MassIVE | Thu Mar 30 23:34:00 BST 2017

SECONDARY ACCESSION(S): PXD004655

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Publications

Extensive cargo identification reveals distinct biological roles of the 12 importin pathways.

Kimura Makoto M Morinaka Yuriko Y Imai Kenichiro K Kose Shingo S Horton Paul P Imamoto Naoko N

eLife 20170124

Vast numbers of proteins are transported into and out of the nuclei by approximately 20 species of importin-β family nucleocytoplasmic transport receptors. However, the significance of the multiple parallel transport pathways that the receptors constitute is poorly understood because only limited numbers of cargo proteins have been reported. Here, we identified cargo proteins specific to the 12 species of human import receptors with a high-throughput method that employs stable isotope labeling w ...[more]

PMID: 28117667

Similar Datasets

SILAC-Tp (12 importins) - Extensive cargo identification reveals distinct biological roles of the 12 importin pathways

Project description:Importin-beta family proteins are nucleocytoplasmic transport receptors (NTRs), and they transport most nuclear proteins as their cargoes into and out of the nuclei. Human cells have 20 species of importin-beta family NTRs, of which 10 (importin-beta, transportin-1, -2, -SR, importin-4, -5, -7, -8, -9, and -11) are nuclear import receptors and 2 (importin-13, and exportin-4) are bi-directional receptors. Here, we identified the import cargo proteins of these 12 NTRs by a method called SILAC-Tp, which employs stable isotope labeling with amino acids in cell culture (SILAC), an in vitro reconstituted transport system, and LC-MS/MS.

2017-01-20 | PXD004655 | Pride

C9orf72 arginine-rich dipeptide repeat proteins disrupt importin beta-mediated nuclear import

Project description:Disruption of nucleocytoplasmic transport (NCT), including mislocalization of the importin beta cargo, TDP-43, is a hallmark of amyotrophic lateral sclerosis (ALS), including ALS caused by a hexanucleotide repeat expansion in C9orf72. However, the mechanism(s) remain unclear. Importin beta and its cargo adaptors have been shown to co-precipitate with the C9orf72-arginine-containing dipeptide repeat proteins (R-DPRs), poly-glycine arginine (GR) and poly-proline arginine (PR), and are protective in genetic modifier screens. Here, we show that R-DPRs interact with importin beta, disrupt its cargo loading, and inhibit nuclear import in permeabilized mouse neurons and HeLa cells, in a manner that can be rescued by RNA. Although R-DPRs induce widespread protein aggregation in this in vitro system, transport disruption is not due to NCT protein sequestration, nor blockade of the phenylalanine-glycine (FG)-rich nuclear pore complex. Our results support a model in which R-DPRs interfere with nuclear transport receptors in the vicinity of the nuclear envelope.

2020-05-20 | PXD015656 | Pride

Expression data of human melanoma cell lines treated with siRNA targeting SR-BI or with the pharmacologic inhibitor BLT-1

Project description:Melanoma patients with high mRNA levels of the HDL receptor SR-BI (SCARB1) reveal poor survival outcome. The aim of the study was to evaluate the role of SR-BI in cancer progression. Therefore, SR-BI was targeted either by siRNA or by using the SR-BI specific lipid transfer inhibitor BLT-1. The SR-BI knockdown specifically revealed reduced protein glycosylation, STAT5 target gene expression and EMT pathway activation. Thus, SR-BI target genes reflect the metastatic phenotype in melanoma cells. We used the transcriptome analysis to compare SR-BI depletion to BLT-1 treatment (which specifically blocks SR-BI mediated lipid transfer) in human melanoma cells.

2018-01-02 | GSE96743 | GEO

Hikeshi-Mediated Nuclear Translocation of HSP70 Promotes Myelinogenesis by Preventing FBXW7-mediated Degradation of Sox10

Project description:Dysregulation of nucleocytoplasmic transport is intensively linked to many neurological diseases. Heat shock proteins 70 (HSP70s), which dramatically change its cellular localization upon stress, play important regulatory roles in nervous system. How the localization of HSP70s is regulated and the underlying physiological functions of this translocation are both poorly understood. Mutation in Hikeshi, encoding a nonconventional nuclear import carrier of HSP70s, lead to inherited leukodystrophy; however, the underlying mechanisms remain poorly understood. Here we showed that Hikeshi and HSP70s are essential for proper CNS myelination and remyelination. Loss of Hikeshi resulted in oligodendrocyte maturation arrest through preventing the nuclear translocation of HSP70s upon oligodendrocyte differentiation. HSP70s interacted with Sox10SOX10 in the nucleus and protected it from E3 ubiquitin ligase FBXW7-mediated ubiquitination degradation. Importantly, we discovered that the Hikeshi-dependent hyperthermia therapy, which induces nuclear import of HSP70s, promoted oligodendrocyte differentiation and remyelination following in vivo demyelinating injury. Overall, we demonstrate that Hikeshi-dependent nuclear translocation of HSP70s is essential for oligodendrocyte differentiation and myelinogenesis, and suggest the potential therapeutic value of hyperthermia therapy in myelin repair.

2023-02-19 | GSE225577 | GEO

Nuclear barrier induction as a new modality of cellular senescence

Project description:Blocking of nucleocytoplasmic trafficking is an essential feature of replicative senescence (RS). However, whether nuclear barrier per se causes cellular senescence still remains elusive. Here, we show that nuclear barrier induced by blocking nucleocytoplasmic trafficking, especially nuclear export, elicits RS-like changes in SA-β-gal activity, DNA damage, and expression of cell cycle regulators. Comparative transcriptome analysis revealed that nuclear barrier-induced senescence (NBIS) was most similar in gene expression changes to RS compared to senescence induced by stresses (oxidative stress, DNA damage and oncogene), implying that nuclear barrier induces RS-like physiological senescence-associated changes. Shared senescence-related processes between NBIS and RS included lysosomal degradation, nuclear transport, and translation, resulting in coordinated reduction in transmission of extrinsic signals to nucleus and intracellular protein supply from nucleus. Notably, these processes were conserved in yeast aging. Therefore, we propose NBIS as a novel modality of cellular senescence, representing the fundamental nature of physiological aging in eukaryotes.

2021-06-17 | GSE112530 | GEO

Knockdown of NUP62 of human head and neck squamous cell carcinoma cell line UMSCC1

Project description:p63, especially its dominant isoform ∆Np63⍺, plays essential roles in squamous cell carcinomas (SCCs); yet the mechanisms controlling its nuclear transport remain unknown. Nucleoporins (NUPs) are a family of proteins building nuclear pore complex (NPC) and mediating nuclear transport across the nuclear envelope. Recent evidence suggests a cell-type-specific function for certain NUPs; however, the significance of NUPs in SCC biology remains unknown. In this study, we report that nucleoporin 62 (NUP62) is highly expressed in stratified squamous epithelia, which is further elevated in SCCs. Depletion of NUP62 inhibited the proliferation ability and augmented differentiation characteristics of SCC cells. This loss of dedifferentiation status was associated with defects in ∆Np63⍺ nuclear transport. We further found that differentiation inducible Rho kinase reduced an interaction between NUP62 and ∆Np63a by phosphorylation of phenylalanine-glycine regions of NUP62, resulting in attenuated ∆Np63⍺ nuclear import. Our results characterize NUP62 as a key gatekeeper for ∆Np63⍺ and uncover its significant function to control ∆Np63⍺ nuclear transport in SCC.

2017-11-16 | GSE103991 | GEO

RASSF1A IS REQUIRED FOR THE MAINTENANCE OF NUCLEAR ACTIN LEVELS

Project description:Nuclear actin participates in many essential cellular processes including gene transcription, chromatic remodelling and mRNA processing. Actin shuttles into and out the nucleus through the action of dedicated transport receptors importin-9 and exportin-6, but how this transport is regulated remains unclear. Here we show that RASSF1A is a novel regulator of actin nucleocytoplasmic trafficking and is required for the active maintenance of nuclear actin levels through supporting binding of exportin-6 (XPO6) to RAN GTPase. RASSF1A (Ras association domain family 1 isoform A) is a tumor suppressor gene frequently silenced by promoter hypermethylation in all major solid cancers. Specifically, we demonstrate that endogenous RASSF1A localizes to the nuclear envelope (NE) and is required for nucleo-cytoplasmic actin transport and the concomitant regulation of Myocardin-related transcription factor A (MRTF-A), a coactivator of the transcription factor serum response factor (SRF). The RASSF1A/RAN/XPO6/nuclear actin pathway is aberrant in cancer cells where RASSF1A expression is lost and correlates with reduced MTRF/SRF activity leading to cell adhesion defects. Taken together, we have identified a previously unknown mechanism by which the nuclear actin pool is regulated and uncovered a previously unknown link of RASSF1A and MTRF/SRF in tumor suppression.

2019-05-30 | PXD011517 | Pride

Proteomic Identification of Nuclear Processes Manipulated by Cytomegalovirus Early during Infection

Project description:Human cytomegalovirus (HCMV) is a herpesvirus that is ubiquitously distributed world-wide and causes life-threating disease upon immunosuppression. HCMV expresses numerous proteins that function to establish an intracellular environment that supports viral replication. Like most DNA viruses, HCMV manipulates processes within the nucleus. We have quantified changes in the host cell nuclear proteome at 24 hpi following infection with a clinical viral isolate. We have combined SILAC with multiple stages of fractionation to define changes. Tryptic peptides were analyzed by RP-HPLC combined with LC-MS/MS on an LTQ Orbitrap Velos massspectrometer. Data from three biological replicates were processed with MaxQuant. A total of 1281 cellular proteins were quantified and 77 were found to be significantly differentially expressed. In addition, we observed 36 viral proteins associated with the nucleus. Diverse biological processes were significantly altered including increased aspects of cell cycling, mRNA metabolism, and nucleocytoplasmic transport while decreased immune responses. We validated changes for several proteins including a subset of classical nuclear transport proteins. In addition, we demonstrated that disruption of these import factors is inhibitory to HCMV replication. Overall, we have identified HCMV-induced changes in the nuclear proteome and uncovered several processes that are important for infection.

2015-06-23 | PXD001909 | Pride

Expression data from the hearts of a mouse model of spontaneous myocardial infarction

Project description:Mice with homozygous null mutations in the HDL receptor (SR-BI) and apoE genes (SR-BI KO/apoE double KO (dKO) mice) spontaneously develop occlusive, atherosclerotic coronary artery disease (CAD) and die prematurely (50% mortality at 42 days of age) on standard chow diet feeding. Microarray analysis was performed to investigate the changes in gene expression profiles during the development of spontaneous severe CAD, which includes myocardial infarction and heart failure. These data will provide new insights in understanding the pathophysiology of CAD. The whole Hearts from dKO or SR-BI+/- apoE-/- (HET) mice (n=9-12) were harvested at 21, 31 and 43 days of age, and analyzed using Affymetrix microarrays. dKO mice do not show detectable signs of CAD at 21 days of age, small myocardial infarction (MI) and heart failure at 31 days of age, and extensive MI and severe heart failure at 43 days of age (50% mortality at 42 days of age). Each mouse was assigned to one array. SR-BI+/- apoE-/- mice (HET) which do not develop detectable signs of CAD on chow diet were used as controls.The data also include those from probucol treated dKO and HET mice (n=2-8).

2013-09-01 | E-GEOD-49937 | biostudies-arrayexpress

Hepatic nonvesicular cholesterol transport is critical for systemic lipid homeostasis

Project description:In cell models, changes in the “accessible” pool of plasma membrane (PM) cholesterol are linked with the regulation of ER sterol synthesis and metabolism by the Aster family of nonvesicular transporters. However, the relevance of such nonvesicular transport mechanisms for lipid homeostasis in vivo has not been defined. Here we reveal two physiological contexts that generate accessible PM cholesterol and engage the Aster pathway in liver: fasting and reverse cholesterol transport (RCT). During fasting, adipose tissue–derived fatty acids activate hepatocyte sphingomyelinase to liberate sequestered PM cholesterol. Aster-dependent cholesterol transport during fasting facilitates cholesteryl ester (CE) formation, cholesterol movement into bile, and VLDL production. During RCT, HDL delivers excess cholesterol to the hepatocyte PM through SR-BI. Loss of hepatic Asters impairs cholesterol movement into feces, raises plasma cholesterol levels, and causes cholesterol accumulation in peripheral tissues. These results reveal fundamental mechanisms by which Aster cholesterol flux contributes to hepatic and systemic lipid homeostasis.

2022-10-24 | GSE206278 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data