PXD056239-1

PXD056239 is an original dataset announced via ProteomeXchange.

Title	Intracellular pH regulates the ubiquitin-mediated degradation of the atypical MAP kinase ERK3
Description	The atypical mitogen-activated protein kinase ERK3 is known for its instability and degradation via the ubiquitin-proteasome system (UPS). However, the specific environmental factors regulating ERK3 turnover have remained unclear. In this study, we demonstrate that intracellular pH (pHi) plays a crucial role in modulating ERK3 stability. We observed that acidification of the extracellular environment significantly increases ERK3 half-life and expression, whereas alkalinization accelerates its degradation. This pH-dependent regulation of ERK3 occurs through the modulation of its ubiquitination by the UPS, with lower pHi reducing ERK3 ubiquitylation and proteasomal degradation. Importantly, this mechanism is consistent across various cell types, highlighting its broad relevance. Moreover, our results suggest that ERK3 stability is not mediated by membrane pH sensors like ASIC1 or TRPV1. Instead, pHi variations directly affect ERK3 stability, likely through protonation-sensitive motifs in its C-terminal region. Furthermore, a proteomic analysis revealed that pH changes globally impact protein stability, including ERK3, suggesting a novel coupling between pH homeostasis and proteome regulation. This study provides critical insights into how pH influences ERK3 turnover and proposes a broader role for pHi in regulating protein stability and cell signaling pathways.
HostingRepository	PRIDE
AnnounceDate	2025-10-07
AnnouncementXML	Submission_2025-10-07_11:07:26.256.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD056239
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Eric Bonneil
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-25 07:12:55	ID requested
⏵ 1	2025-10-07 11:07:26	announced

10.6019/PXD056239;

submitter keyword: MAP kinases

ERK3

pH

protein stability

Sylvain meloche
contact affiliation	IRIC-Université de Montréal
contact email	sylvain.meloche@umontreal.ca
lab head
Eric Bonneil
contact affiliation	Proteomic Platform
contact email	eric.bonneil@umontreal.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056239
     1. Label: PRIDE project
     2. Name: Intracellular pH regulates the ubiquitin-mediated degradation of the atypical MAP kinase ERK3