PXD052527-1

PXD052527 is an original dataset announced via ProteomeXchange.

Title	E3 ligase substrate adaptor SPOP fine tunes the UPR of pancreatic beta cells
Description	The Cullin 3 E3 ligase adaptor protein, SPOP, targets proteins for ubiquitination and proteasomal degradation. We previously established the β cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β cell specific Spop deletion mouse strain (SpopβKO) and found that Spop is necessary to prevent aberrant basal insulin secretion and for maintaining glucose- stimulated insulin secretion (GSIS) through impacts on glycolysis and glucose-stimulated calcium flux. Integration of proteomic, TF-regulatory gene network and biochemical analyses identified XBP1 as a functionally important SPOP substrate in pancreatic β cells.Further, loss of SPOP strengthened the IRE1α-XBP1 axis of unfolded protein response (UPR) signaling. ER stress promoted proteasomal degradation of SPOP, supporting a model whereby SPOP fine-tunes XBP1 activation during the UPR. These results position SPOP as a regulatorof β cell function and proper UPR activation.
HostingRepository	PRIDE
AnnounceDate	2024-11-12
AnnouncementXML	Submission_2024-11-12_08:36:26.056.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hossein Fazelinia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-23 11:43:52	ID requested
⏵ 1	2024-11-12 08:36:26	announced

Dataset with its publication pending

submitter keyword: E3 ligase , PDX1,SPOP, proteasomal degradation, diabetes

Doris A.
contact affiliation	Smilow Center for Translational Research 12-124 3400 Civic Center Blvd Philadelphia, PA 19104 P: 215-573-5413 F: 215-898-5408
contact email	stoffers@pennmedicine.upenn.edu
lab head
Hossein Fazelinia
contact affiliation	Children's Hospital of Philadelphia
contact email	fazeliniah@email.chop.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/11/PXD052527

PRIDE project URI

• PRIDE
  1. PXD052527
     1. Label: PRIDE project
     2. Name: E3 ligase substrate adaptor SPOP fine tunes the UPR of pancreatic beta cells