PXD065932

PXD065932 is an original dataset announced via ProteomeXchange.

Title	Hepatocyte nuclear factor 1a controls the proliferation of pancreatic beta-cells by regulating the expression of a Golgi-associated protein
Description	HNF1A gene encodes a transcription factor hepatocyte nuclear factor 1α (HNF1α), and mutations in this gene cause maturity-onset diabetes of the young type 3 (MODY3), which is characterized by impaired insulin secretion. Previous studies have shown that HNF1α controls the proliferation and number of pancreatic β-cells. However, the molecular mechanism by which HNF1α regulates β-cell growth remains unclear. Here, we demonstrate that TMED6 (transmembrane p24 trafficking protein 6), a transmembrane protein involved in transport processes at the ER-Golgi interface, is a novel HNF1α target in pancreatic β-cells. TMED6 expression was decreased in the β-cells of Hnf1a knockout (KO) mice. Suppressing TMED6 in mouse MIN6 β-cells reduced cell growth. Conversely, overexpression of TMED6 rescued the proliferation of Hnf1a knockdown (KD) MIN6 cells. Furthermore, TMED6 KO mice fed a high-fat diet exhibited reduced β-cell mass and impaired insulin secretion. Biochemical studies revealed that TMED6 controls β-cell proliferation by regulating the proteasomal degradation of GOLGA2, a Golgi-associated protein that regulates cell proliferation. Overexpression of GOLGA2 restored proliferation in both Hnf1a KD and Tmed6 KD MIN6 cells. Taken together, our results indicate that HNF1α controls pancreatic β-cell proliferation via the TMED6-GOLGA2 axis. We performed proteome analyses of control and Tmed6 KD MIN6 cells in triplicate.
HostingRepository	jPOST
AnnounceDate	2026-07-09
AnnouncementXML	Submission_2026-07-08_08:00:10.726.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Koshi Imami
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidomethyl-L-cysteine; unknown modification
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-09 00:10:21	ID requested
⏵ 1	2026-07-08 08:00:11	announced

Dataset with its publication pending

submitter keyword: HNF1a, Golgi, Pancreatic beta-cells

Yoshifumi Sato
lab head
Koshi Imami
contact affiliation	RIKEN
dataset submitter

jPOST dataset URI

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