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PXD066332

PXD066332 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMarch5-mediated Trim28 degradation preserves islet β-cell function in mice
DescriptionInsulin 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.
HostingRepositoryPRIDE
AnnounceDate2025-07-24
AnnouncementXMLSubmission_2025-07-24_01:37:18.128.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYangshan Chen
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-07-20 04:23:35ID requested
12025-07-24 01:37:18announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: islet transplantation, MafA, Kindlin-2,insulin secretion, glucose intolerance
Contact List
Huiling Cao
contact affiliationDepartment of Biochemistry, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology,
contact emailcaohl@sustech.edu.cn
lab head
Yangshan Chen
contact affiliationThe Eighth Affiliated Hospital, Sun Yat-sen University
contact emailchyshan2@mail2.sysu.edu.cn
dataset submitter
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Dataset FTP location
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