MassIVE MSV000097003

Partial Public PXD060380

VIPER-TACs leverage viral E3 ligases for disease-specific targeted protein degradation

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Description

In targeted protein degradation (TPD) a protein of interest is degraded by chemically induced proximity to an E3 ubiquitin ligase. One limitation of using TPD therapeutically is that most E3 ligases have broad tissue expression, which can contribute to toxicity via target degradation in healthy cells. Many pathogenic and oncogenic viruses encode E3 ligases (vE3s), which de facto have strictly limited expression to diseased cells. Here, we provide proof-of-concept for Viral E3 Pan-Essential Removing Targeting Chimeras (VIPER-TACs) that are bi-functional molecules that utilize viral E3 ubiquitin ligases to selectively degrade pan-essential proteins and eliminate diseased cells. We find that the human papillomavirus (HPV) ligase E6 can degrade the SARS1 pan-essential target protein in a model of HPV-positive cervical cancer to selectively kill E6 expressing cancer cells. Thus, VIPER-TACs have the capacity to dramatically increase the therapeutic window, alleviate toxicity concerns, and ultimately expand the potential target space for TPD. [doi:10.25345/C5NG4H436] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: targeted protein degradation, viral E3 ligase ; DatasetType:Proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Patrick Ryan Potts, Amgen Research, USA
Submitting User: jliu19
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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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