Work

Cytosolic Delivery of Functional Ubiquitin

Year: 2025

Type: article

Abstract: ABSTRACT The proteostasis network involves complex protein signaling cascades. The tagging of proteins with ubiquitin is central to the degradation of cellular proteins, but understanding its exact role in processing proteins is complicated by the complexity and extent of its utilization within cells. Here, we describe the application of a traceless protein delivery strategy to effect the uptake of exogenous ubiquitin into the cytosol of human cells. We find that coadministration of the endosomolytic peptides L17E and, especially, L17ER4 provides not only cytosolic access to ubiquitin but also its functional incorporation into endogenous proteins. By enabling the study of semisynthetic ubiquitin variants in the human cytosol, this strategy could advance the field of ubiquitin biology.

Source: Journal of Peptide Science

DOI: 10.1002/psc.70026

Authors: JoLynn B. Giancola, Aniekan Okon, Yanfeng Li, Eric R. Strieter, Ronald T. Raines

Institutions: Massachusetts Institute of Technology, University of Massachusetts Amherst

Language: English

Topic: Ubiquitin and proteasome pathways

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,030

Funders: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences