Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

STRIPAK directs PP2A activity to promote oncogenic transformation

ABSTRACT: We evaluated the effects of suppressing MAP4K4 on transcriptome and YAP1 pathway based on the observation that partial suppression of MAP4K4 leads to transformation through activation of YAP1. Mutations and deletions involving subunits of the serine-threonine phosphatase PP2A occur in a broad range of human cancers, and partial loss of PP2A function contributes to cell transformation. In particular, displacement of regulatory B subunits by the viral oncoprotein SV40 small-t antigen (ST) or mutation or deletion of PP2A subunits alters the abundance and types of PP2A complexes in cells and induces cell transformation in human cells. Here we show that ST not only displaces common PP2A B subunits but also promotes PP2A A-C subunit interactions with a set of alternative B subunits (B’’’, striatins) that are components of the Striatin-interacting phosphatase and kinase (STRIPAK) complex. We found that members of the STRIPAK complex are required for ST-PP2A induced cell transformation. PP2A interacts with and dephosphorylates the STRIPAK-associated kinase MAP4K4, which induces cell transformation in part through the regulation of the Hippo pathway effector YAP1. These observations identify an unanticipated role of MAP4K4 in transformation and show that the STRIPAK complex plays a key role in defining PP2A specificity and activity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE118272 | GEO | 2019/12/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Kim et al. STRIPAK directs PP2A activity towards MAP4K4 to promote oncogenic transformation

Project description:STRIPAK directs PP2A activity towards MAP4K4 to promote oncogenic transformation

2019-10-04 | MSV000084422 | MassIVE

STRIPAK directs PP2A activity to promote oncogenic transformation

Project description:STRIPAK directs PP2A activity to promote oncogenic transformation

| PRJNA485011 | ENA

A. nidulans STRIPAK - Assembly of a heptameric STRIPAK complex is required for coordination of light-dependent multicellular fungal development with secondary metabolism in Aspergillus nidulans

Project description:Eukaryotic striatin forms striatin-interacting phosphatase and kinase (STRIPAK) complexes that control many cellular processes including development, cellular transport, signal transduction, stem cell differentiation and cardiac functions. However, detailed knowledge of complex assembly and its roles in stress responses are currently poorly understood. Here, we discovered six striatin (StrA) interacting proteins, which form a heptameric complex in the filamentous fungus Aspergillus nidulans. The main components are: scaffold StrA (striatin), further components SipA (Mob3), SipB (SIKE-like), SipC (STRIP1/2), SipD (SLMAP), catalytic (SipE, PP2Ac) and regulatory (SipF, PP2AA) phosphatase subunits. The STRIPAK complex, which is established during vegetative growth and maintained during the early hours of light and dark development, is formed on the nuclear envelope in the presence of scaffold StrA. The loss of striatin revealed three STRIPAK subcomplexes: (I) SipA only interacts with StrA, (II) SipB-SipD is found as a heterodimer, (III) SipC, SipE and SipF exist as a heterotrimeric complex.

2019-03-12 | PXD011927 | Pride

The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii

Project description:Phenotypic switching from tachyzoite to bradyzoite and vice versa is the fundamental mechanism underpinning the pathogenicity and adaptability of the protozoan parasite Toxoplasma gondii. Accumulation of cytoplasmic starch granules is a hallmark of the quiescent bradyzoite stage. The regulatory factors and mechanisms that contribute to amylopectin storage in bradyzoites remain incompletely known. Here, we show that T. gondii protein phosphatase 2A (PP2A) holoenzyme is composed of a catalytic subunit (PP2A-C), a structural subunit (PP2A-A) and a regulatory subunit (PP2A-B). Disruption of any of these subunits increased starch accumulation and disrupted the parasite differentiation. The putative PP2A holoenzyme substrates were identified by phosphoproteomics. PP2A contributes to the regulation of amylopectin metabolism via dephosphorylation of calcium-dependent protein kinase 2 at S679. Several putative PP2A substrates were found to play important roles in bradyzoite differentiation. Our findings establish PP2A as an integral component of the regulatory network mediating amylopectin metabolism and tachyzoite-bradyzoite transformation in T. gondii.

2022-11-05 | PXD033120 | Pride

PP2A is essential for Th17 differentiaiton

Project description:Phosphatase PP2A expression level is positively correlated to the clinical severity of systemic lupus erythematosus (SLE) and IL17A cytokine overproduction, indicating a potential role of PP2A in controlling TH17 differentiation and inflammation. By generating a mouse strain with the ablation of the catalytic subunit α of PP2A in peripheral mature T cells (PP2A cKO), we provide evidence here that PP2A complex is essential in TH17 differentiation. Hence, PP2A cKO mice exhibited a selective reduction of TH17 cell numbers and an attenuated disease severity in an experimental autoimmune encephalomyelitis (EAE) model. Importantly, PP2A deficiency ablated c-terminal phosphorylation of SMAD2 whereas increased c-terminal phosphorylation of SMAD3. Through direct binding to and regulating the activity of RORγt, the phosphorylational changes of these R-SMADs subsequently reduced Il17a transcription. Finally, PP2A inhibitors recapitulated the phenotype of PP2A cKO mice, i.e., inhibiting TH17 differentiation and protecting mice from EAE. Together, the current study proves that phosphatase PP2A is essential for TH17 differentiation, and inhibition of PP2A could be a possible therapeutic approach for the controlling of TH17-driven autoimmune diseases.

2018-09-13 | GSE119836 | GEO

RAS and PP2A activities converge on epigenetic gene regulation [BS-Seq]

Project description:RAS-mediated human cell transformation requires inhibition of the tumor suppressor Protein Phosphatase 2A (PP2A). Both RAS and PP2A mediate their effects by phosphoregulation, but phosphoprotein targets and cellular processes in which RAS and PP2A activities converge in human cancers have not been systematically analyzed. Here, based on mass spectrometry phosphoproteome data we discover that phosphosites co-regulated by RAS and PP2A are enriched on proteins involved in epigenetic gene regulation. As examples, RAS and PP2A co-regulate the same phosphorylation sites on HDAC1/2, KDM1A, MTA1/2, RNF168 and TP53BP1. Mechanistically, we validate co-regulation of NuRD chromatin repressor complex by RAS and PP2A. Consistent with their known synergistic effects in cancer, RAS activation and PP2A inhibition resulted in epigenetic reporter de-repression and activation of oncogenic transcription. Notably, transcriptional de-repression by PP2A inhibition was associated with increased euchromatin and decrease in global DNA methylation. Further, targeting of RAS- and PP2A-regulated epigenetic proteins decreased viability of KRAS-mutant human lung cancer cells. Collectively the results indicate that epigenetic protein complexes involved in oncogenic gene expression constitute a significant point of convergence for RAS hyperactivity and PP2A inhibition in cancer. Further, this work provides a resource for future studies focusing on phosphoregulation as a previously unappreciated layer of regulation of epigenetic gene regulation in cancer, and in other RAS/PP2A-regulated cellular processes.

2023-02-06 | GSE220592 | GEO

RAS and PP2A activities converge on epigenetic gene regulation [RNA-Seq]

2023-02-06 | GSE220591 | GEO

RAS and PP2A activities converge on epigenetic gene regulation [ATAC-Seq]

2023-02-06 | GSE220590 | GEO

Effect of depletion of IntS4, IntS6, mts, or Pp2A-29B on gene expression in Drosophila DL1 cells

Project description:To investigate the effect of depletion of Integrator complex subunits IntS4, IntS6, mts, or Pp2A-29B on gene expression

2023-11-10 | GSE223974 | GEO

Catalytic Subunit of Protein Phosphatase 2A (PP2Ac) Influences the Meiosis Initiation During Spermatocyte Meiosis Prophase I

Project description:As a serine/threonine phosphatase, protein phosphatase 2A (PP2A) is essential in numerous physiological processes. Our previously study confirmed PP2A dysfunction can cause azoospermia by generating catalytic subunit of PP2A (Ppp2ca) conditional knockout (CKO) in C57BL/6J mice. Here, we further explored the possible mechanisms by focusing on meiosis initiation and spermatogenesis. The deficiency of Ppp2ca in germ cells conspicuously disturbed spermatogonial differentiation and lead to pachytene arrest, accompanied by defects in programmed double-strand break (DSB) repair and meiotic sex chromosome inactivation (MSCI). Furthermore, Ppp2ca-deficient spermatocytes exhibited abnormal agglutination and cohesion complex degradation of chromosome, probably contributing to pachytene arrest. Our study demonstrates the irreplaceable role of PP2A in spermatogenesis and provide more evidences on azoospermia etiology.

2021-12-01 | GSE181132 | 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