SUMOylation of GMFB regulates its stability and function in retinal pigment epithelial cells under hyperglycemia.

Autor: Sun W; Department 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., Wang J; Department of Ophthalmology of Shanghai Tongji Hospital and Laboratory of Clinical Visual Science of Tongji Eye Institute, Tongji University, Shanghai 200065, China; Department of Medical Genetics, School of Medicine, Tongji University, Shanghai 200065, China., Liu C; Department 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., Gao F; Department 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., Ou Q; Department of Ophthalmology of Shanghai Tongji Hospital and Laboratory of Clinical Visual Science of Tongji Eye Institute, Tongji University, Shanghai 200065, China; Department of Pharmacology, School of Medicine, Tongji University, Shanghai 200065, China., Tian H; Department 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., Xu J; Department 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., Zhang J; Department of Ophthalmology of Shanghai Tongji Hospital and Laboratory of Clinical Visual Science of Tongji Eye Institute, Tongji University, Shanghai 200065, China; Department of Pharmacology, School of Medicine, Tongji University, Shanghai 200065, China., Li J; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200065, China., Xu J; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200065, China., Jia S; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200065, China., Zhang J; Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200025, China., Xu G; Department of Ophthalmology of Shanghai Tongji Hospital and Laboratory of Clinical Visual Science of Tongji Eye Institute, Tongji University, Shanghai 200065, China; Department of Pharmacology, School of Medicine, Tongji University, Shanghai 200065, China. Electronic address: gtxu@tongji.edu.cn., Huang J; Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: jyhuanj@shsmu.edu.cn., Jin C; Department 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. Electronic address: 12060@tongji.edu.cn., Lu L; Department 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. Electronic address: lulixia@tongji.edu.cn.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 May; Vol. 268 (Pt 2), pp. 131678. Date of Electronic Publication: 2024 Apr 22.
DOI: 10.1016/j.ijbiomac.2024.131678
Abstrakt: 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).
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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