PXD043686

PXD043686 is an original dataset announced via ProteomeXchange.

Title	UBXN1 maintains ER proteostasis and represses UPR activation by modulating translation
Description	ER protein homeostasis (proteostasis) is essential to facilitate proper folding and maturation of proteins in the secretory pathway. Loss of ER proteostasis can lead to the accumulation of misfolded or aberrant proteins in the ER and triggers the unfolded protein response (UPR). Here we find that the p97 adaptor UBXN1 is an important negative regulator of the UPR. Loss of UBXN1 sensitizes cells to ER stress and activates canonical UPR signaling pathways. This in turn leads to widespread upregulation of the ER stress transcriptional program. Using comparative, quantitative proteomics we show that deletion of UBXN1 results in a significant enrichment of proteins involved in ER-quality control processes including those involved in protein folding and import. Notably, we find that loss of UBXN1 does not perturb p97-dependent ER associated degradation. Our studies indicate that loss of UBXN1 increases translation in both resting and ER-stressed cells. Surprisingly, this process is independent of p97 function. Taken together, our studies have identified a new role for UBXN1 in repressing translation and maintaining ER proteostasis in a p97 independent manner.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:45:37.883.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-11 13:09:58	ID requested
1	2024-06-16 01:11:05	announced
⏵ 2	2024-10-22 06:45:38	announced	2024-10-22: Updated project metadata.

Ahlstedt BA, Ganji R, Mukkavalli S, Paulo JA, Gygi SP, Raman M, UBXN1 maintains ER proteostasis and represses UPR activation by modulating translation. EMBO Rep, 25(2):672-703(2024) [pubmed]

10.1038/s44319-023-00027-z;

submitter keyword: UBXN, TMT, UPR, ER stress, proteostasis

Malavika Raman
contact affiliation	Dept. of Developmental Molecular and Chemical Biology Tufts University School of Medicine Boston MA
contact email	malavika.raman@tufts.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043686
     1. Label: PRIDE project
     2. Name: UBXN1 maintains ER proteostasis and represses UPR activation by modulating translation