{"database":"JPOST Repository","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Raw":["https://storage.jpostdb.org/JPST003927/files/20250626_480_DIA_CB_MM_Control_4.raw","https://storage.jpostdb.org/JPST003927/files/20250626_480_DIA_CB_MM_Tmed6_KD_Number2_2.raw","https://storage.jpostdb.org/JPST003927/files/20250626_480_DIA_CB_MM_Control_1.raw","https://storage.jpostdb.org/JPST003927/files/20250626_480_DIA_CB_MM_Tmed6_KD_Number2_3.raw","https://storage.jpostdb.org/JPST003927/files/20250626_480_DIA_CB_MM_Tmed6_KD_Number2_4.raw","https://storage.jpostdb.org/JPST003927/files/20250626_480_DIA_CB_MM_Control_3.raw","https://storage.jpostdb.org/JPST003927/files/20250626_480_DIA_CB_MM_Tmed6_KD_Number2_1.raw","https://storage.jpostdb.org/JPST003927/files/20250626_480_DIA_CB_MM_Control_2.raw"],"Other":["https://storage.jpostdb.org/JPST003927/files/DIA-NN_output.zip"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Yoshifumi Sato"],"species":["Mus Musculus (mouse)"],"full_dataset_link":["https://repository.jpostdb.org/entry/JPST003927"],"submitter_affiliation":["RIKEN"],"sample_protocol":[""],"repository":["jPOST"],"data_protocol":[""],"additional_accession":[]},"is_claimable":false,"name":"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.  \n\nWe performed proteome analyses of control and Tmed6 KD MIN6 cells in triplicate.","dates":{"publication":"Thu Jul 09 00:00:00 BST 2026"},"accession":"PXD065932","cross_references":{"TAXONOMY":["10090"]}}