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CBX4 stabilizes NEUROD1 through SUMO-ubiquitin crosstalk to delay β-cell senescence

ABSTRACT: CBX4 expression is progressively lost in aged and diabetic pancreatic β-cells, correlating with cellular senescence. Mechanistically, CBX4 stabilizes NEUROD1 by promoting its SUMOylation at lysine 38, which antagonizes NEDD4-mediated ubiquitination. Stabilized NEUROD1 enhances insulin transcription and activates CaMKII signaling by suppressing Camk2n1 expression. This cascade preserves mitochondrial function and calcium homeostasis in β-cells. Thus, the STAT5A-CBX4-NEUROD1 axis represents a key protective pathway against β-cell aging and a potential therapeutic target for T2DM.

ORGANISM(S): Mus Musculus

SUBMITTER: Liang Jin

PROVIDER: PXD079253 | iProX | Thu Jun 04 00:00:00 GMT+01:00 2026

REPOSITORIES: iProX

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