New ProteomeXchange dataset PXD069857

[ProteomeCentral Agent]

Dear ProteomeXchange subscriber, a new ProteomeXchange dataset is being announced. To see more information, click here:

https://proteomecentral.proteomexchange.org/dataset/PXD069857

Summary of dataset

Status: new
Identifier: PXD069857
HostingRepository: PRIDE
Species: Homo sapiens
Title: QPCT-PDIA4 rescues ΔF508 and N1303K CFTR function in cystic fibrosis
Submitter: Le Sun
LabHead: John Yates
Description: Cystic fibrosis (CF) is a genetic disorder caused by CFTR mutations, most commonly ΔF508, leading to defective ion transport and multisystem pathology. Small-molecule modulators partially restore mutant CFTR function, but therapeutic efficacy remains limited, particularly for N1303K mutation refractory to current treatments. Here, we show that inhibition of the glutaminyl-peptide cyclotransferase (QPCT)-dependent pathway rescues both the surface expression and functional activity of ΔF508 CFTR. Integrated molecular and physiological analyses identify protein disulfide-isomerase A4 (PDIA4) as a key mediator of this rescue via its pyroglutamate (pGlu)-dependent interaction with ΔF508 CFTR, which is essential for surface trafficking. Furthermore, inhibition of QPCT also restores the function of the N1303K CFTR mutant, revealing a broader mechanistic relevance of this pathway in correcting CFTR misfolding and trafficking defects. These findings uncover a generalizable mec
hanism for correcting CFTR folding abnormalities and suggest new therapeutic strategies for mutations unresponsive to existing modulators.

HTML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD069857
XML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD069857&outputMode=XML