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

Wan Sun; Juan Wang; Caiying Liu; Furong Gao; Qingjian Ou; Haibin Tian; Jingying Xu; Jieping Zhang; Jiao Li; Jie Xu; Song Jia; Jingfa Zhang; GuoTong Xu; Jian Huang; Caixia Jin; Lixia Lu

doi:10.1016/j.ijbiomac.2024.131678

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

Int J Biol Macromol. 2024 Apr 22;268(Pt 2):131678. doi: 10.1016/j.ijbiomac.2024.131678. Online ahead of print.

Authors

Wan Sun¹, Juan Wang², Caiying Liu¹, Furong Gao¹, Qingjian Ou³, Haibin Tian¹, Jingying Xu¹, Jieping Zhang³, Jiao Li⁴, Jie Xu⁴, Song Jia⁴, Jingfa Zhang⁵, GuoTong Xu⁶, Jian Huang⁷, Caixia Jin⁸, Lixia Lu⁹

Affiliations

¹ 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.
² 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.
³ 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.
⁴ Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200065, China.
⁵ Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200025, China.
⁶ 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.
⁷ Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: jyhuanj@shsmu.edu.cn.
⁸ 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.
⁹ 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.

PMID: 38657921
DOI: 10.1016/j.ijbiomac.2024.131678

Abstract

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).

Keywords: Glia maturation factor-β (GMFB); Hyperglycemia; Protein stability; Retinal pigment epithelial cells; SUMOylation.