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Related Concept Videos

The Proteasome01:13

The Proteasome

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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.
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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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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.
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The Proteasome Structure01:17

The Proteasome Structure

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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...
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Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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Anaphase Promoting Complex00:50

Anaphase Promoting Complex

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The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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Related Experiment Video

Updated: Mar 21, 2026

Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology
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Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology

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A cascading activity-based probe sequentially targets E1-E2-E3 ubiquitin enzymes.

Monique P C Mulder1, Katharina Witting1, Ilana Berlin1

  • 1Division of Cell Biology, Netherlands Cancer Institute, Amsterdam, the Netherlands.

Nature Chemical Biology
|May 17, 2016
PubMed
Summary
This summary is machine-generated.

Researchers developed UbDha, a novel probe that tracks ubiquitin (Ub) and ubiquitin-like modifier (Ubl) enzymes. This tool identifies active enzymes in cellular processes, aiding in the study of ubiquitination.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Biology

Background:

  • Post-translational modifications, including ubiquitination (Ub) and ubiquitin-like modifications (Ubls), are crucial for regulating cellular processes.
  • These modifications are mediated by complex enzymatic cascades involving E1, E2, and E3 enzymes.

Purpose of the Study:

  • To develop a novel tool for monitoring the activity of Ub and Ubl modifying enzymes.
  • To enable the detection and study of catalytically active enzymes within these cascades.

Main Methods:

  • Development of a cascading activity-based probe, termed UbDha.
  • UbDha mimics the natural Ub pathway, undergoing sequential trans-thioesterifications with E1, E2, and E3 enzymes.
  • Irreversible reaction of UbDha with active site cysteine residues of target enzymes for detection.

Main Results:

  • UbDha successfully 'hops' and 'traps' catalytically active Ub-modifying enzymes, distinguishing them from their substrates.
  • The probe's mechanism is adaptable for studying various Ubls.
  • Demonstrated utility for proteome-wide profiling and monitoring enzyme activity in living cells.

Conclusions:

  • UbDha provides a versatile and novel methodology for interrogating Ub and Ubl cascades.
  • The probe is amenable to structural studies and offers new tools for understanding enzyme function in cellular pathways.