Video Experimental Relacionado

Updated: Sep 10, 2025

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

La doble funcionalidad de MDM2 en los PROTAC amplía los horizontes de la degradación proteica dirigida

Junyi Zhao¹, Hongzhen Chen¹, Chao Liang^2,3

¹Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, China.

Biomarker research

|August 27, 2025

Resumen

Las quimeras dirigidas a la proteólisis (PROTAC) aprovechan el doble minuto 2 del ratón (MDM2) para la degradación de proteínas dirigida. Los diseños optimizados de PROTAC apuntan o aprovechan las estrategias terapéuticas avanzadas de MDM2 para diversas enfermedades.

Área de la Ciencia:

La bioquímica
Biología molecular
Química medicinal

Sus antecedentes:

La degradación dirigida de proteínas (TPD) utiliza quimeras dirigidas a la proteólisis (PROTAC) para degradar las proteínas.
El doble minuto 2 del ratón (MDM2) es crucial en las vías de la enfermedad y puede actuar como una ligasa E3 o una proteína diana.

Objetivo del estudio:

Para explorar el potencial terapéutico de los PROTAC que utilizan MDM2.
Revisar las estrategias para optimizar los PROTAC que aprovechan o se dirigen a MDM2.

Principales métodos:

Diseño de las moléculas de PROTAC heterobifuncionales.
Utilizando la actividad de la ligasa E3 de MDM2 o dirigiéndose directamente a MDM2.
Optimización de la selección de ojivas, propiedades de enlace y reclutadores de ligasa E3.

Principales resultados:

Los PROTAC que aprovechan la actividad de la ligasa E3 de MDM2 degradan con éxito las proteínas diana.
Los PROTAC que se dirigen directamente a MDM2 ofrecen nuevas vías terapéuticas.
Los estudios in vitro e in vivo demuestran un éxito significativo.

Conclusiones:

Los avances en el diseño de PROTAC amplían el alcance de TPD.
Los PROTAC basados en MDM2 optimizados aceleran el desarrollo de nuevos tratamientos para enfermedades.

Palabras clave:

Proyecto de puente El Homo-PROTAC MDM2 (en inglés)Protección de la salud pública TPD y sus derivados

Más Videos Relacionados

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes

Published on: January 12, 2024

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Videos de Conceptos Relacionados

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...

Export of Misfolded Proteins out of the ER

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...

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...

Translocation of Proteins into the Mitochondria

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...

The Proteasome Structure

The Proteasome Structure

The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...

Peptide Identification Using Tandem Mass Spectrometry

Peptide Identification Using Tandem Mass Spectrometry

Tandem mass spectrometry, also known as MS/MS or MS2, is an analytical technique that employs two mass analyzers. Essentially it is a series of mass spectrometers that helps isolate a particular biomolecule and then helps study its chemical properties.
This technique helps gather information regarding the protein from which the peptide was obtained and to study the peptides’ amino acid sequence. Identifying peptides from a complex mixture is an important component of the growing field of...