E3 ubiquitin ligase RNF128 promotes Lys63-linked polyubiquitination on SRB1 in macrophages and aggravates atherosclerosis

Yapeng Liu, Xinyu Zhang, Liwen Yu, Lei Cao, Jie Zhang, Qian Li, Xiaohong Wang, Wenqian Qi, Liangyu Cai, Ruiqing Ren, Weiwei Wang, Xiaobin Guo, Guohai Su, Bo Xi, Yun Zhang, Chengjiang Gao (), Meng Zhang () and Cheng Zhang ()
Additional contact information
Yapeng Liu: Qilu Hospital of Shandong University
Xinyu Zhang: Qilu Hospital of Shandong University
Liwen Yu: Qilu Hospital of Shandong University
Lei Cao: Qilu Hospital of Shandong University
Jie Zhang: Qilu Hospital of Shandong University
Qian Li: Qilu Hospital of Shandong University
Xiaohong Wang: Qilu Hospital of Shandong University
Wenqian Qi: Qilu Hospital of Shandong University
Liangyu Cai: Qilu Hospital of Shandong University
Ruiqing Ren: Qilu Hospital of Shandong University
Weiwei Wang: Qilu Hospital of Shandong University
Xiaobin Guo: Central Hospital Affiliated to Shandong First Medical University
Guohai Su: Central Hospital Affiliated to Shandong First Medical University
Bo Xi: Shandong University
Yun Zhang: Qilu Hospital of Shandong University
Chengjiang Gao: Shandong University
Meng Zhang: Qilu Hospital of Shandong University
Cheng Zhang: Qilu Hospital of Shandong University

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract Macrophage-derived foam cell formation is the hallmark of atherosclerotic plaques prominently attributed to excessive lipid uptake and metabolic disorders. As a classic membrane-localized ubiquitin ligase, the role of RNF128 in atherosclerosis remains unknown. We discover that RNF128 is specifically expressed in macrophages of the lipid core based on single-cell RNA sequencing data and persistent hyperlipidemia induces the high expression of RNF128 in macrophages. RNF128 ablation in macrophages ameliorates atherosclerosis in both male and female mice under the background of ApoE and LDLR deficiency. Mechanistically, RNF128 directly binds to scavenger receptor B1 (SRB1), preventing its degradation through the lysosomal system and promoting oxidized low-density lipoprotein (oxLDL)-induced foam cell formation and inflammatory response in macrophages. In addition, RNF128 catalyzes Lys63-linked polyubiquitination on the cytoplasmic C-terminus of the SRB1 at lysine 478, which promotes the endosome SRB1 recycling to the cell membrane with the assistance of Rab11, instead of entering the lysosome for degradation.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57404-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57404-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57404-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().