Evidence map›Paper›PMID 41581872›Full record

ArticleThe Journal of biological chemistry2026

Engineering an orthogonal ubiquitin transfer cascade with RING E3 RNF38 by phage display to reveal its regulation of nuclear transport.

Li Zhou, In Ho Jeong, Hang Li, Nicolas Rios, Jing Zhang, Xiaoyu Wang, Shu Liu, Yayun Xie, Wei Wei, Geon H Jeong and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Li ZhouDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
In Ho JeongDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
Hang LiDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
Nicolas RiosDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
Jing ZhangDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA; Department of Biology, Georgia State University, Atlanta, Georgia, USA.
Xiaoyu WangDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
Shu LiuDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
Yayun XieDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
Wei WeiNeuroscience Institute, Georgia State University, Atlanta, Georgia, USA.
Geon H JeongDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
Duc DuongDepatrment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA.
Nicholas T SeyfriedDepatrment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA.
Bingzhong XueDepartment of Biology, Georgia State University, Atlanta, Georgia, USA.
Hang ShiDepartment of Biology, Georgia State University, Atlanta, Georgia, USA.
Angela M MabbNeuroscience Institute, Georgia State University, Atlanta, Georgia, USA.
Yiyang WangDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China. Electronic address: wangyiyang@jnu.edu.cn.
Hiroaki KiyokawaDepartment of Pharmacology, Northwestern University, Chicago, Illinois, USA. Electronic address: kiyokawa@northwestern.edu.
Jun YinDepartment of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA. Electronic address: junyin@gsu.edu.

Funding

Protein ubiquitination and deubiquitination in neurological disordersR01NS136464 · NINDS · GEORGIA STATE UNIVERSITY · PI Angela M Mabb · 2025 to 2026
$811k
Protein ubiquitination and deubiquitination in neurological disordersR56NS136464 · NINDS · GEORGIA STATE UNIVERSITY · PI MABB, ANGELA M · 2024 to 2024
$390k
NINDS NIH HHS R01 NS136464NINDS NIH HHS R56 NS136464
6 · The paper itself

Abstract

RING E3 ubiquitin (UB) ligases rely on signature RING domains for mediating UB transfer to substrate proteins. The large number of RING E3s and their weak association with substrates pose a significant challenge in identifying the substrates of individual E3s, thereby hindering the elucidation of their biological functions. Here, we utilized phage display to engineer an "orthogonal UB transfer" (OUT) cascade with RING E3 RNF38, enabling the exclusive transfer of an engineered UB (xUB) to its substrates in the cell. The OUT screen revealed RNF38 substrates regulating nucleocytoplasmic transport (Ran, RanGAP1, and KPNA2), protein translation (HuR and Rack1), and endosomal sorting (VPS35). Furthermore, RNF38-catalyzed ubiquitination was found to induce the degradation of the substrate proteins and negatively affect the translocation of transcription factors E2F1 and phosphorylated STAT3 (p-STAT3) into the nucleus. Phage selection of the RNF38 RING library also revealed hotspot residues for E2 interaction, which may guide the engineering of orthogonal E2-E3 pairs with other RING E3s. Overall, our work discovered new roles of RNF38 in regulating nuclear transport and established an anchoring point for expanding OUT cascades within the large family of RING E3s for revealing their UB transfer targets and cellular functions.

Indexed as

Active Transport, Cell NucleusPeptide LibraryProtein EngineeringUbiquitinUbiquitin-Protein LigasesHumansUbiquitinationPeptide LibraryUbiquitinUbiquitin-Protein LigasesE3 ubiquitin ligasephage displayprotein engineeringRING domainubiquitin

Identifiers

PMID41581872
PMCPMC12945521

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.