Dataset Information

Inhibition of MUL1-mediated ubiquitination promotes mitochondria-associated translation

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Fibroblast, Blood

DISEASE(S): Breast Cancer

SUBMITTER: Christian Heckendorf

LAB HEAD: Valentina Perissi

PROVIDER: PXD030187 | Pride | 2025-09-08

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	1.GPS2_Mito_K63_TMT_mqpar.xml	Xml
	1.GPS2_Mito_K63_TMT_txt.zip	Other
	2.SILAC_K63_proteome_2X_mqpar.xml	Xml
	2.SILAC_K63_proteome_2X_txt.zip	Other
	2.SILAC_K63_proteome_mqpar.xml	Xml

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Publications

Inhibition of K63 ubiquitination by G-Protein pathway suppressor 2 (GPS2) regulates mitochondria-associated translation.

Gao Yuan Y Kwan Julian J Orofino Joseph J Burrone Giulia G Mitra Sahana S Fan Ting-Yu TY English Justin J Hekman Ryan R Emili Andrew A Lyons Shawn M SM Cardamone Maria Dafne MD Perissi Valentina V

Pharmacological research 20240731

G-Protein Pathway Suppressor 2 (GPS2) is an inhibitor of non-proteolytic K63 ubiquitination mediated by the E2 ubiquitin-conjugating enzyme Ubc13. Previous studies have associated GPS2-mediated restriction of ubiquitination with the regulation of insulin signaling, inflammatory responses and mitochondria-nuclear communication across different tissues and cell types. However, a detailed understanding of the targets of GPS2/Ubc13 activity is lacking. Here, we have dissected the GPS2-regulated K63 ...[more]

PMID: 39094987

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