PXD052214

PXD052214 is an original dataset announced via ProteomeXchange.

Title	DYRK1B phosphorylates FOXO1 to promote hepatic gluconeogenesis
Description	Dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B), a member of the CMGC group of kinase, is associated with metabolic syndrome. However, the molecular mechanisms involved remain elusive. In this study, we demonstrate that Dyrk1b expression is induced in liver by fasting and in diabetic mice. Using both in vivo and in vitro studies, we show that DYRK1B promotes hepatic gluconeogenesis and glucose intolerance. Liver-specific Dyrk1b conditional knockout mice were protected from diet-induced hyperglycemia. Mechanistically, DYRK1B interacts with and phosphorylates FOXO1, primarily at Thr467/Ser468, which is essential for its nuclear localization. Additionally, DYRK1B inhibits AKT mediated FOXO1 phosphorylation at Thr24 and Ser256, thereby enhancing its nuclear retention. DYRK1B mediated phosphorylation enhances the expression of gluconeogenic genes and promotes gluconeogenesis. Further, a pharmacological inhibitor of DYRK1B significantly reduced blood glucose levels in diabetic mice. Collectively, these findings offer new insights into DYRK1B’s role in the glucose metabolism and identify it as a new therapeutic target for treating diabetes.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-06_16:01:19.237.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shanshan Li
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-13 05:55:11	ID requested
⏵ 1	2025-05-06 16:01:20	announced

Li S, Huang K, Xu C, Zhang H, Wang X, Zhang R, Lu Y, Mohan M, Hu C, DYRK1B phosphorylates FOXO1 to promote hepatic gluconeogenesis. Nucleic Acids Res, 53(8):(2025) [pubmed]

10.1093/nar/gkaf319;

submitter keyword: DYRK1B, Diabetes, FOXO1,Gluconeogenesis, Phosphorylation

Cheng Hu
contact affiliation	Shanghai Diabetes Institute, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
contact email	alfredhc@sjtu.edu.cn
lab head
Shanshan Li
contact affiliation	Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
contact email	lynn1991@alumni.sjtu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052214
     1. Label: PRIDE project
     2. Name: DYRK1B phosphorylates FOXO1 to promote hepatic gluconeogenesis