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Published on: May 5, 2021
SUMOylation of GMFB regulates its stability and function in retinal pigment epithelial cells under hyperglycemia
Wan Sun1, Juan Wang2, Caiying Liu1
1Department of Ophthalmology of Shanghai Tongji Hospital and Laboratory of Clinical Visual Science of Tongji Eye Institute, Tongji University, Shanghai 200065, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200065, China.
Background:
Glia maturation factor beta (GMFB) is a growth and differentiation factor that acts as an intracellular regulator of signal transduction pathways. The small ubiquitin-related modifier (SUMO) modification, SUMOylation, is a posttranslational modification (PTM) that plays a key role in protein subcellular localization, stability, transcription, and enzymatic activity. Recent studies have highlighted the importance of SUMOylation in the inflammation and progression of numerous diseases. However, the relationship between GMFB and SUMOylation is unclear.
Results:
Here, we report for the first time that GMFB and SUMO1 are markedly increased in retinal pigment epithelial (RPE) cells at the early stage of diabetes mellitus (DM) under hyperglycemia. The GMFΒ protein could be mono-SUMOylated by SUMO1 at the K20, K35, K58 or K97 sites. SUMOylation of GMFB led to its increased protein stability and subcellular translocation. Furthermore, deSUMOylation of GMFΒ downregulates multiple signaling pathways, including the Jak-STAT signaling pathway, p38 pathway and NF-kappa B signaling pathway.
Conclusions:
This work provides novel insight into the role of SUMOylated GMFB in RPE cells and provides a novel therapeutic target for diabetic retinopathy (DR).
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