PXD030187-1

PXD030187 is an original dataset announced via ProteomeXchange.

Title	Inhibition of MUL1-mediated ubiquitination promotes mitochondria-associated translation
Description	G-Protein Pathway Suppressor 2 (GPS2) is an inhibitor of non-proteolytic ubiquitination mediated by the E2 ubiquitin-conjugating enzyme Ubc13. Previous studies have associated GPS2-mediated restriction of K63 ubiquitination with the regulation of insulin signaling, inflammatory responses and mitochondria-nuclear communication across many different tissues and cell types. However, a detailed understanding of the targets of GPS2/Ubc13 activity is currently lacking. Here, we have dissected the GPS2-regulated K63 ubiquitome in mouse embryonic fibroblasts and human breast cancer cells, unexpectedly finding an enrichment for proteins involved in RNA binding and translation. Characterization of putative targets, including the RNA-binding protein PABPC1 and translation factor eiF3m, revealed a strategy for regulating the mitochondria-associated translation of selected mRNAs via MUL1-mediated ubiquitination. Our data indicate that removal of GPS2-mediated inhibition, either via genetic deletion or stress-induced nuclear translocation, promotes the ubiquitination of mitochondria-associated translation factors leading to increased expression of an adaptive antioxidant program. In light of GPS2 role in nuclear-mitochondria communication, these findings reveal an exquisite regulatory network for modulating mitochondrial gene expression through spatially coordinated transcription and translation.
HostingRepository	PRIDE
AnnounceDate	2025-09-08
AnnouncementXML	Submission_2025-09-07_17:06:46.097.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Heckendorf
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-05 04:54:19	ID requested
⏵ 1	2025-09-07 17:06:46	announced

10.1016/j.phrs.2024.107336;

Gao Y, Kwan J, Orofino J, Burrone G, Mitra S, Fan TY, English J, Hekman R, Emili A, Lyons SM, Cardamone MD, Perissi V, Inhibition of K63 ubiquitination by G-Protein pathway suppressor 2 (GPS2) regulates mitochondria-associated translation. Pharmacol Res, 207():107336(2024) [pubmed]

submitter keyword: LC-MSMUbiquitin,i.e. Human, PABPC, mitochondria stress response (MSR)S, Plasma, mitochondria, MUL1, GPS2, Liver

Valentina Perissi
contact affiliation	Boston University
contact email	vperissi@bu.edu
lab head
Christian Heckendorf
contact affiliation	Boston University
contact email	heckend@bu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030187
     1. Label: PRIDE project
     2. Name: Inhibition of MUL1-mediated ubiquitination promotes mitochondria-associated translation