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Related Concept Videos

Regulated Protein Degradation02:58

Regulated Protein Degradation

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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...
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The Proteasome02:18

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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.
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Covalently Linked Protein Regulators02:04

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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Protein Complexes with Interchangeable Parts01:57

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Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
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Proteins: From Genes to Degradation02:11

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.
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Regulation of Expression at Multiple Steps01:23

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Updated: Sep 14, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
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Programmed Targeted Protein Degradation Via DNA Modularized Ligand.

Xuanming Teng1, Jingyi Yang1, Zhiyi Ren1

  • 1School of Pharmacy, Shanghai Key Laboratory of Chemical Biology, East China University of Science and Technology, 130 Mei Long Road, Shanghai, 200237, China.

Chemmedchem
|July 23, 2025
PubMed
Summary

This study introduces DNA-PROTACs, a modular approach to protein degradation. This method simplifies the design and screening of proteolysis targeting chimeras (PROTACs) for therapeutic development.

Keywords:
DNA modulizationDNA self‐assemblyPROTACstargeted protein degradation

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

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Proteolysis targeting chimeras (PROTACs) offer a novel therapeutic modality for targeted protein degradation.
  • Current PROTAC development faces challenges in chemical synthesis and linker optimization.

Purpose of the Study:

  • To present a proof-of-concept for a modular DNA-PROTAC method.
  • To demonstrate a DNA-based ligand modularization strategy for PROTAC construction.
  • To facilitate programmatic discovery of new PROTAC molecules.

Main Methods:

  • Construction and validation of DNA-PROTACs targeting bromodomain-containing protein 4 (BRD4) and silent mating type information regulation 2 homolog-2 (Sirt2).
  • Assessment of BRD4 degradation kinetics in HeLa cells using time-course experiments.
  • Systematic introduction of design, synthesis, and mechanism of action for BRD4 and Sirt2 DNA-PROTACs.

Main Results:

  • Successful identification and validation of functional BRD4 and Sirt2 DNA-PROTACs.
  • Demonstration of DNA-PROTACs' effectiveness in targeted protein degradation.
  • Establishment of a modular DNA-based platform for PROTAC development.

Conclusions:

  • The DNA-PROTAC strategy offers a promising new approach for PROTAC development.
  • This method may streamline linker design and ligand screening processes for PROTACs.
  • The findings pave the way for accelerated discovery of novel protein degradation therapeutics.