Evidence map›Paper›PMID 38450154›Full record

ArticleiScience2024

Mapping the substrate landscape of protein phosphatase 2A catalytic subunit PPP2CA.

Abigail Brewer, Gajanan Sathe, Billie E Pflug, Rosemary G Clarke, Thomas J Macartney, Gopal P Sapkota

Open access · goldAbstract read
In one paragraph

Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

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  13. The mTOR pathway controls phosphorylation of BRAF at T401.Cell communication and signaling : CCS · 2024
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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

6 authors at 1 institution in 1 country.

Abigail BrewerMedical Research Council (MRC) Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Gajanan SatheMedical Research Council (MRC) Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Billie E PflugMedical Research Council (MRC) Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Rosemary G ClarkeMedical Research Council (MRC) Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Thomas J MacartneyMedical Research Council (MRC) Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Gopal P SapkotaMedical Research Council (MRC) Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
University of Dundee · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Protein phosphatase 2A (PP2A) is an essential Ser/Thr phosphatase. The PP2A holoenzyme complex comprises a scaffolding (A), regulatory (B), and catalytic (C) subunit, with PPP2CA being the principal catalytic subunit. The full scope of PP2A substrates in cells remains to be defined. To address this, we employed dTAG proteolysis-targeting chimeras to efficiently and selectively degrade dTAG-PPP2CA in homozygous knock-in HEK293 cells. Unbiased global phospho-proteomics identified 2,204 proteins with significantly increased phosphorylation upon dTAG-PPP2CA degradation, implicating them as potential PPP2CA substrates. A vast majority of these are novel. Bioinformatic analyses revealed involvement of the potential PPP2CA substrates in spliceosome function, cell cycle, RNA transport, and ubiquitin-mediated proteolysis. We identify a pSP/pTP motif as a predominant target for PPP2CA and confirm some of our phospho-proteomic data with immunoblotting. We provide an in-depth atlas of potential PPP2CA substrates and establish targeted degradation as a robust tool to unveil phosphatase substrates in cells.

Indexed as

EnzymologyProperties of biomoleculesProteinProteomics

Identifiers

PMID38450154
PMCPMC10915630
OpenAlexW4391943230

What Socratic holds

Textmetadata
LicenceCC BY
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.