Direct Protein Degradation: Emerging Tools to Probe Biological Complexity in Mammalian Systems

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Main Authors: Sailasree Rajalekshmi, Kizhakke Mattada Sathyan
Format: Artículo Open Access
Published: Wiley 2025
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author Sailasree Rajalekshmi
Kizhakke Mattada Sathyan
author_facet Sailasree Rajalekshmi
Kizhakke Mattada Sathyan
Sailasree Rajalekshmi
Kizhakke Mattada Sathyan
collection Wiley Open Access
contents Direct Protein Degradation: Emerging Tools to Probe Biological Complexity in Mammalian Systems Sailasree Rajalekshmi Kizhakke Mattada Sathyan BioEssays ABSTRACT Conditional degron approaches for acute and reversible protein depletion have become standard tools for studying gene function in cells and model organisms. Traditional gene perturbation methods have advanced gene function studies but are limited by slow kinetics, potential irreversibility, and lethality when targeting essential genes. To overcome these limitations, tag‐based and antibody‐based direct protein degradation technologies have been developed. These direct protein degradation systems utilize endogenous protein degradation pathways to achieve rapid and reversible protein depletion. When combined with genome editing, these systems provide precise temporal—and in some cases, spatial—control over endogenous protein expression. In this review, we will discuss the current status of tag‐based and antibody‐based direct protein degron technologies. We aim to provide a comprehensive guide for selecting these tools, highlighting their context‐dependent applications and potential improvements to enhance efficiency and reliability. 10.1002/bies.70075 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/bies.70075
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institution Wiley Open Access
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publishDate 2025
publisher Wiley
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spellingShingle Direct Protein Degradation: Emerging Tools to Probe Biological Complexity in Mammalian Systems
Sailasree Rajalekshmi
Kizhakke Mattada Sathyan
BioEssays
Direct Protein Degradation: Emerging Tools to Probe Biological Complexity in Mammalian Systems Sailasree Rajalekshmi Kizhakke Mattada Sathyan BioEssays ABSTRACT Conditional degron approaches for acute and reversible protein depletion have become standard tools for studying gene function in cells and model organisms. Traditional gene perturbation methods have advanced gene function studies but are limited by slow kinetics, potential irreversibility, and lethality when targeting essential genes. To overcome these limitations, tag‐based and antibody‐based direct protein degradation technologies have been developed. These direct protein degradation systems utilize endogenous protein degradation pathways to achieve rapid and reversible protein depletion. When combined with genome editing, these systems provide precise temporal—and in some cases, spatial—control over endogenous protein expression. In this review, we will discuss the current status of tag‐based and antibody‐based direct protein degron technologies. We aim to provide a comprehensive guide for selecting these tools, highlighting their context‐dependent applications and potential improvements to enhance efficiency and reliability. 10.1002/bies.70075 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Direct Protein Degradation: Emerging Tools to Probe Biological Complexity in Mammalian Systems
topic BioEssays
url https://onlinelibrary.wiley.com/doi/10.1002/bies.70075