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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

Lysosomes

Lysosomes

Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...

Lysosomal Hydrolases

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...

Proteins: From Genes to Degradation

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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...

Proteins: From Genes to Degradation

Proteins: From Genes to Degradation

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Related Experiment Video

Updated: Feb 13, 2026

Use of MRI-ultrasound Fusion to Achieve Targeted Prostate Biopsy

Use of MRI-ultrasound Fusion to Achieve Targeted Prostate Biopsy

Published on: April 9, 2019

Development of Prostate-Specific Lysosome-Targeting Degraders.

Deqin Cai¹, Xuankun Chen¹, Yaxian Zhou¹

¹Lachman Institute of Pharmaceutical Development, School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53705, United States.

Journal of the American Chemical Society

|February 11, 2026

Summary

This summary is machine-generated.

Researchers developed a new targeted protein degradation (TPD) strategy for prostate cancer, using PSMA to target lysosomes. This method effectively degrades membrane and extracellular proteins, offering new precision medicine avenues.

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Last Updated: Feb 13, 2026

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Tuning Degradation to Achieve Specific and Efficient Protein Depletion

Tuning Degradation to Achieve Specific and Efficient Protein Depletion

Published on: July 20, 2019

Area of Science:

Biochemistry
Molecular Biology
Oncology

Background:

Targeted protein degradation (TPD) is a promising therapeutic approach for various diseases.
Current TPD strategies are limited in degrading membrane and extracellular proteins.

Purpose of the Study:

To develop a novel lysosome-targeting degradation strategy for prostate cancer.
To utilize Prostate-Specific Membrane Antigen (PSMA) as a lysosome-targeting receptor (LTR).

Main Methods:

Developed PSMA TArgeting Chimeras (PTACs) for lysosomal degradation.
Tested PTACs for degradation of extracellular and membrane proteins in prostate cancer cells.
Evaluated degradation potency and selectivity of specific PTACs (Ctx-L3, Atz-L5).

Main Results:

Demonstrated selective, potent, rapid, and sustained lysosomal degradation of target proteins.
Achieved exceptional degradation potencies for EGFR (4.3 pM) and PD-L1 (2 pM) using Ctx-L3 and Atz-L5.
Showcased the versatility of PTACs in antibody- and small-molecule formats for PD-L1 degradation.

Conclusions:

The PTAC platform enables effective lysosomal degradation of extracellular and membrane proteins in prostate cancer.
This approach advances TPD technology for precision medicine in prostate-related diseases.