PXD037703

PXD037703 is an original dataset announced via ProteomeXchange.

Title	A degradation motif in STAU1 defines a novel family of proteins involved in inflammation
Description	Cancer development is regulated by inflammation. Staufen 1 (STAU1) is an RNA-binding protein whose expression level is critical in cancer cells as it is related to cell proliferation or cell death. STAU1 expression levels are downregulated during mitosis due to its degradation by the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C). In this paper, we map the molecular determinant involved in STAU1 degradation in mitosis to amino acids 38-50 and, by alanine scanning, we shorten the motif to F39PxPxxLxxxxL50 (FPL-motif). Mutation of the FPL-motif prevents STAU1 degradation by APC/C. Interestingly, a search in databases reveals that the FPL-motif is shared by 15 additional proteins most of them being involved in inflammation. We show that one of these proteins, MAP4K1, is indeed degraded via the FPL-motif; however, it is not a target of APC/C. Using proximity labeling with STAU1, we identify TRIM25, an E3-ubiquitin ligase involved in the innate immune response and interferon production, as responsible for STAU1 and MAP4K1 degradation, dependent on the FPL-motif. These results are consistent with previous studies that linked STAU1 to cancer-induced inflammation and identify a novel degradation motif that likely coordinates a novel family of proteins involved in inflammation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:30:32.293.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD037703
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Eric Bonneil
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	LTQ FT

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-25 04:39:34	ID requested
1	2023-02-21 09:30:47	announced
⏵ 2	2023-11-14 07:30:33	announced	2023-11-14: Updated project metadata.

10.6019/PXD037703;

Gonzalez Quesada Y, DesGroseillers L, A Degradation Motif in STAU1 Defines a Novel Family of Proteins Involved in Inflammation. Int J Mol Sci, 23(19):(2022) [pubmed]

submitter keyword: Staufen 1

human

inflammation

protein degradation

E3-ubiquitin ligase

degron

TRIM25

Luc Desgroseillers
contact affiliation	Université de Montréal
contact email	luc.desgroseillers@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. PXD037703
     1. Label: PRIDE project
     2. Name: A degradation motif in STAU1 defines a novel family of proteins involved in inflammation