Evidence map›Paper›PMID 21044074›Full record

ArticleJournal of neurochemistry2010

Regulation of protein phosphatase 2A methylation by LCMT1 and PME-1 plays a critical role in differentiation of neuroblastoma cells.

Jean-Marie Sontag, Viyada Nunbhakdi-Craig, Martina Mitterhuber, Egon Ogris, Estelle Sontag

Open access · greenAbstract readComparative Study
In one paragraph

Article in Journal of neurochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.5field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 59 citations in OpenAlex.

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  16. NNMT Silencing Activates Tumor Suppressor PP2A, Inactivates Oncogenic STKs, and Inhibits Tumor Forming Ability.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
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  20. Deregulation of the protein phosphatase 2A, PP2A in cancer: complexity and therapeutic options.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 3 countries.

Jean-Marie SontagSchool of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, Callaghan, NSW, Australia. estelle.sontag@newcastle.edu.au
Viyada Nunbhakdi-Craig
Martina Mitterhuber
Egon Ogris
Estelle Sontag
The University of Texas Southwestern Medical Center · USMax Perutz Labs · AT

Funding

Role of PP2A in tauopathiesR01AG018883 · NIA · UT SOUTHWESTERN MEDICAL CENTER · PI SONTAG, ESTELLE · 2001 to 2006
$1.3M
Role of PP2A in TauopathiesR56AG018883 · NIA · UT SOUTHWESTERN MEDICAL CENTER · PI SONTAG, ESTELLE · 2007 to 2007
$406k
NIA NIH HHS AG18883NIA NIH HHS R01 AG018883NIA NIH HHS R56 AG018883
6 · The paper itself

Abstract

Neuritic alterations are a major feature of many neurodegenerative disorders. Methylation of protein phosphatase 2A (PP2A) catalytic C subunit by the leucine carboxyl methyltransferase (LCMT1), and demethylation by the protein phosphatase methylesterase 1, is a critical PP2A regulatory mechanism. It modulates the formation of PP2A holoenzymes containing the Bα subunit, which dephosphorylate key neuronal cytoskeletal proteins, including tau. Significantly, we have reported that LCMT1, methylated C and Bα expression levels are down-regulated in Alzheimer disease-affected brain regions. In this study, we show that enhanced expression of LCMT1 in cultured N2a neuroblastoma cells, which increases endogenous methylated C and Bα levels, induces changes in F-actin organization. It promotes serum-independent neuritogenesis and development of extended tau-positive processes upon N2a cell differentiation. These stimulatory effects can be abrogated by LCMT1 knockdown and S-adenosylhomocysteine, an inhibitor of methylation reactions. Expression of protein phosphatase methylesterase 1 and the methylation-site L309Δ C subunit mutant, which decrease intracellular methylated C and Bα levels, block N2a cell differentiation and LCMT1-mediated neurite formation. Lastly, inducible and non-inducible knockdown of Bα in N2a cells inhibit process outgrowth. Altogether, our results establish a novel mechanistic link between PP2A methylation and development of neurite-like processes.

Indexed as

AnimalsCarboxylic Ester HydrolasesCatalytic DomainCell DifferentiationCell Line, TumorCells, CulturedDNA MethylationGene Knockdown TechniquesMiceNeuritesNeuroblastomaProtein O-MethyltransferaseProtein Phosphatase 2Carboxylic Ester HydrolasesLCMT1 protein, humanLcmt1 protein, mouseProtein O-MethyltransferaseProtein Phosphatase 2protein phosphatase methylesterase-1

Identifiers

PMID21044074
PMCPMC3057931
OpenAlexW1494691627

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.