SUMOylation 修饰调控 GMFB 在高糖环境下的稳定性及其在视网膜色素上皮细胞中的功能。

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

机构信息

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.

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.

出版信息

Int J Biol Macromol. 2024 May;268(Pt 2):131678. doi: 10.1016/j.ijbiomac.2024.131678. Epub 2024 Apr 22.

DOI:10.1016/j.ijbiomac.2024.131678

PMID:38657921

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).

摘要

背景

胶质细胞成熟因子β（GMFB）是一种生长和分化因子，作为细胞内信号转导途径的调节剂。小泛素相关修饰物（SUMO）修饰，SUMOylation，是一种翻译后修饰（PTM），在蛋白质亚细胞定位、稳定性、转录和酶活性中起着关键作用。最近的研究强调了 SUMOylation 在许多疾病的炎症和进展中的重要性。然而，GMFB 和 SUMOylation 之间的关系尚不清楚。

结果

在这里，我们首次报道在高血糖的糖尿病早期，视网膜色素上皮（RPE）细胞中 GMFB 和 SUMO1 的表达明显增加。GMFΒ 蛋白可在 K20、K35、K58 或 K97 位点被 SUMO1 单 SUMOylation。GMFB 的 SUMOylation导致其蛋白稳定性和亚细胞易位增加。此外，GMFΒ 的去 SUMOylation 下调多个信号通路，包括 Jak-STAT 信号通路、p38 通路和 NF-κB 信号通路。