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Regulated Protein Degradation

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...

Regulated Protein Degradation

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...

The Proteasome

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...

The Proteasome

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...

Proteins: From Genes to Degradation

Proteins: From Genes to Degradation

Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA molecules by RNA...

Proteins: From Genes to Degradation

Proteins: From Genes to Degradation

Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA molecules by RNA...

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Related Experiment Video

Updated: May 15, 2026

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

Biomolecular Condensates as Protein Degradation Tools for Intracellular Targets.

Yi Li^1,2, Zhicheng Jin³, Sharif U Ahmed¹

¹Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.

Nature Communications

|May 13, 2026

Summary

Researchers developed antibody-enriched biomolecular condensates for targeted protein degradation. These novel tools selectively eliminate disease-causing proteins like KRAS G12V, offering a versatile platform for cancer therapy without genetic modification.

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Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates

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Published on: January 5, 2024

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High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

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Published on: November 9, 2020

Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates

Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates

Published on: January 5, 2024

Area of Science:

Biochemistry
Molecular Biology
Cell Biology

Background:

Targeted protein degradation is a promising therapeutic strategy.
Current methods face challenges in achieving phenotype-specific degradation across cell types.

Purpose of the Study:

To develop a novel intracellular protein degradation tool using antibody-enriched biomolecular condensates.
To demonstrate selective degradation of oncogenic KRAS G12V and tumor growth suppression.

Main Methods:

Formation of antibody-enriched biomolecular condensates via liquid-liquid phase separation.
Incorporation of proteasome-targeting motifs into condensate precursors.
Loading condensates with mutation-specific antibodies for targeted substrate clearance.
In vitro and in vivo assessment of KRAS G12V degradation and tumor growth inhibition.

Main Results:

Biomolecular condensates facilitate cytosolic trafficking and direct proteasome recruitment.
Condensates selectively degrade oncogenic KRAS G12V in heterozygous cells.
Tumor growth was suppressed in a KRAS G12V xenograft model.
The platform demonstrated improved delivery uniformity and preserved antibody activity.

Conclusions:

Antibody-enriched biomolecular condensates represent a modular and adaptable platform for targeted protein degradation.
This strategy offers a non-genetic approach for precise elimination of disease-causing proteins.
The system shows potential for developing new cancer therapies by targeting specific protein mutations.