Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Zinc binds to and directly inhibits protein phosphatase 2A in vitro.

ABSTRACT: Zinc induces protein phosphatase 2A (PP2A) inactivation and tau hyperphosphorylation through PP2A (tyrosine 307) phosphorylation in cells and the brain, but whether Zn(2+) has a direct inhibitory effect on PP2A is not clear. Here we explored the effect of Zn(2+) on PP2A and their direct interaction in vitro. The results showed that Zn(2+) mimicked the inhibitory effect of okadaic acid on protein phosphatase and prevented tau dephosphorylation in N2a cell lysates. PP2A activity assays indicated that a low concentration (10 μmol/L) of Zn(2+) inhibited PP2A directly. Further Zn(2+)-IDA-agarose affinity binding assays showed that Zn(2+) bound to and inhibited PP2Ac(51-270) but not PP2Ac(1-50) or PP2Ac(271-309). Taken together, Zn(2+) inhibits PP2A directly through binding to PP2Ac(51-270) in vitro.

SUBMITTER: Xiong Y

PROVIDER: S-EPMC5563689 | biostudies-other | 2015 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Protein phosphatase 2A interacts with and directly dephosphorylates RelA.

Project description: Not available

| S-EPMC2665282 | biostudies-literature

TIP30 directly binds p53 tumor suppressor protein in vitro.

Project description: Not available

| S-EPMC3887794 | biostudies-literature

Cancerous inhibitor of Protein Phosphatase 2A promotes B-cell activation in vitro

Project description:The generation of optimal immune response requires combined activation of both T- and B-cells. Here, we demonstrate that the cancerous inhibitor of protein phosphatase 2A (CIP2A) is a novel factor that governs activation of both T- and B-cells in vivo. Upon ovalbumin challenge, CIP2A-deficient (CIP2AHOZ) mice show impaired immune response. Furthermore, CIP2AHOZ mice had impaired clearance of Listeria Monocytogenesis (L.m.) infection, combined with decreased numbers of CD8+ T-cells and IFN-γ secretion. In an ovalbumin model of allergic asthma, CIP2AHOZ B-cells were impaired in IgE and IgG secretion, despite of normal Th2 differentiation and unaffected numbers of inflammatory cells or cytokines in bronchoalveolar lavage. Importantly, the cell-autonomous effect of CIP2A deficiency for both T- and B-cell activation was confirmed by in vitro assays. During the T-cell activation CIP2A, was shown to promote expression of ETS-1, whereas in B-cells CIP2A loss resulted in inhibition of MYC-mediated gene expression. Together these results identify CIP2A as a novel cell-autonomous regulator governing both T- and B-cell activation in vivo. They also identify CIP2AHOZ as a novel murine model for investigation of impaired immune response and allergic asthma.

2015-12-01 | GSE63391 | GEO

Erlotinib derivative inhibits hepatocellular carcinoma by targeting CIP2A to reactivate protein phosphatase 2A.

Project description: Not available

| S-EPMC4123111 | biostudies-literature

B56alpha/protein phosphatase 2A inhibits adipose lipolysis in high-fat diet-induced obese mice.

Project description: Not available

| S-EPMC2940515 | biostudies-literature

Melatonin directly binds and inhibits death-associated protein kinase 1 function in Alzheimer's disease.

Project description: Not available

| S-EPMC7890046 | biostudies-literature

An antiapoptotic protein, c-FLIPL, directly binds to MKK7 and inhibits the JNK pathway.

Project description: Not available

| S-EPMC1679768 | biostudies-literature

The zinc finger antiviral protein directly binds to specific viral mRNAs through the CCCH zinc finger motifs.

Project description: Not available

| S-EPMC525010 | biostudies-other

Synaptic released zinc promotes tau hyperphosphorylation by inhibition of protein phosphatase 2A (PP2A).

Project description: Not available

| S-EPMC3322889 | biostudies-other

Piperacetazine directly binds to the PAX3::FOXO1 fusion protein and inhibits its transcriptional activity

Project description:The tumor-specific chromosomal translocation product, PAX3::FOXO1, is an aberrant fusion protein that plays a key role for oncogenesis in the alveolar subtype of rhabdomyosarcoma (RMS). PAX3::FOXO1 represents a validated molecular target for alveolar RMS and successful inhibition of its oncogenic activity is likely to have significant clinical applications. Even though several PAX3::FOXO1 function-based screening studies have been successfully completed, a directly binding small molecule inhibitor of PAX3::FOXO1 has not been reported. Therefore, we screened small molecule libraries to identify compounds that were capable of directly binding to PAX3::FOXO1 protein using surface plasmon resonance technology. Compounds that directly bound to PAX3::FOXO1 were further evaluated in secondary transcriptional activation assays. We discovered that piperacetazine can directly bind to PAX3::FOXO1 protein and inhibit fusion protein-derived transcription in multiple alveolar RMS cell lines. Piperacetazine inhibited anchorage-independent growth of fusion positive alveolar RMS cells but not embryonal RMS cells. Based on our findings, piperacetazine is a molecular scaffold upon which derivatives could be developed as specific inhibitors of PAX3::FOXO1. These novel inhibitors could potentially be evaluated in future clinical trials for recurrent or metastatic alveolar RMS as novel targeted therapy options.

2023-09-12 | GSE242690 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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