PXD066332-1

PXD066332 is an original dataset announced via ProteomeXchange.

Title	March5-mediated Trim28 degradation preserves islet β-cell function in mice
Description	Insulin deficiency from β-cell dysfunction underpins both type 1 and type 2 diabetes. However, the regulatory pathways underlying β-cell function remain incompletely understood. Here, we identify that March5 and Trim28 as key modulators of β-cell function. March5 is downregulated and Trim28 upregulated in islets from human or mouse with impaired glucose tolerance. Loss of March5 in β-cells impairs insulin production and glucose tolerance, while its overexpression improves both. Mechanistically, March5 inhibits Trim28 by targeting it for ubiquitination, thereby preventing Trim28-mediated Kindlin-2 degradation, which elevates MafA and insulin expression in male mice. Trim28 deletion in β-cells rescues glucose intolerance in March5-deficient male mice, highlighting their joint regulatory pathway. Furthermore, March5 and Kindlin-2 double haploinsufficiency significantly impair insulin production and glucose tolerance, underscoring their shared pathway. Importantly, islet transplantation with March5-overexpressing or Trim28-deficient β-cells effectively ameliorates glucose intolerance in streptozotocin-induced diabetic male mice. In conclusion, our results suggest that targeting the March5/Trim28/Kindlin-2/MafA pathway may offer a promising therapeutic strategy to restore β-cell function in diabetes.
HostingRepository	PRIDE
AnnounceDate	2025-07-24
AnnouncementXML	Submission_2025-07-24_01:37:18.128.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yangshan Chen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-20 04:23:35	ID requested
⏵ 1	2025-07-24 01:37:18	announced

Dataset with its publication pending

submitter keyword: islet transplantation, MafA, Kindlin-2,insulin secretion, glucose intolerance

Huiling Cao
contact affiliation	Department of Biochemistry, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology,
contact email	caohl@sustech.edu.cn
lab head
Yangshan Chen
contact affiliation	The Eighth Affiliated Hospital, Sun Yat-sen University
contact email	chyshan2@mail2.sysu.edu.cn
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/2025/07/PXD066332

PRIDE project URI

• PRIDE
  1. PXD066332
     1. Label: PRIDE project
     2. Name: March5-mediated Trim28 degradation preserves islet β-cell function in mice