PXD021598

PXD021598 is an original dataset announced via ProteomeXchange.

Title	Regulation of PP2A-subfamily holoenzyme function by carboxyl-terminal methylation
Description	The family of Phosphoprotein Phosphatases (PPPs) is responsible for most cellular serine and threonine dephosphorylation. PPPs achieve substrate specificity and selectivity by forming multimeric holoenzymes with catalytic, scaffolding, and regulatory subunits. Although there are only ten catalytic PPP subunits encoded in the human genome, the formation of holoenzymes creates hundreds of unique enzymes that oppose kinases and carry out specific dephosphorylation reactions. Thus, to achieve the correct cellular phosphorylation state, the assembly of PPP holoenzymes needs to be tightly controlled. Indeed, changes in the cellular repertoire of PPPs are frequently linked to human disease, including cancer and neurodegeneration. The Protein Phosphatase 2A (PP2A) subfamily of PPPs consists of PP2A, PP4, PP6, and holoenzyme formation is at least in part regulated by carboxyl (C)-terminal methyl-esterification (often referred to as methylation) of the catalytic subunits. This reversible modification is catalyzed by a Leucine Carboxyl Methyltransferase-1 (LCMT1) that utilizes S-adenosyl-methionine (SAM) as the methyl donor and removed by Protein Phosphatase Methylesterase 1 (PME1). For PP2A, C-terminal methylation controls regulatory subunit selection. Notably, different types of regulatory subunits display differential methylation sensitivity. For PP4 and PP6, the role of C-terminal methylation is less well defined. Here, we use mass spectrometry-based proteomics, methylation-ablating mutations, and genome editing to comprehensively elucidate the role of C-terminal methylation in PP2A, PP4, and PP6 function in multiple cell lines. Using these approaches, we quantitatively determine the effects of reduced C-terminal methylation on PP2A, PP4, and PP6 holoenzyme assembly in an unbiased, isoform-specific manner.
HostingRepository	MassIVE
AnnounceDate	2021-11-29
AnnouncementXML	Submission_2021-11-29_07:33:37.929.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Mark Adamo
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl; Oxidation; Methyl; TMT6plex
Instrument	Q Exactive Plus; Orbitrap Fusion; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-21 12:14:23	ID requested
⏵ 1	2021-11-29 07:33:38	announced

no publication

submitter keyword: PP2A, methylation, c-terminal methylation, phosphoprotein phosphatase, PPP, serine dephosphorylation, threonine dephosphorylation, holoenzyme, cancer, neurodegeneration, PP4, PP6, Leucine Carboxyl Methyltransferase-1, LCMT1, S-adenosyl-methionine, SAM, Protein Phosphatase Methylesterase 1, PME1

Arminja Kettenbach
contact affiliation	The Geisel School of Medicine at Dartmouth
contact email	arminja.n.kettenbach@dartmouth.edu
lab head
Mark Adamo
contact affiliation	Dartmouth College
contact email	mark.e.adamo@dartmouth.edu
dataset submitter

MassIVE dataset URI

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