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Updated: May 11, 2026
09:25
Quantifying Subcellular Ubiquitin-proteasome Activity in the Rodent Brain
Published on: May 21, 2019
Proteasome regulation by ADP-ribosylation
Park F Cho-Park1, Hermann Steller
1Strang Laboratory of Apoptosis and Cancer Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
Cell
|April 30, 2013
Summary
ADP-ribosylation enhances 26S proteasome activity by modifying PI31, a regulator. This process involves tankyrase (TNKS) and promotes the assembly of the 26S proteasome, crucial for cell survival and linked to diseases.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The ubiquitin-proteasome system (UPS) is vital for cellular homeostasis, degrading ubiquitinated proteins.
- Dysfunctions in the UPS are implicated in diseases like cancer and neurodegenerative disorders.
- The 26S proteasome is the primary proteolytic machine within the UPS.
Purpose of the Study:
- To investigate the role of ADP-ribosylation in regulating 26S proteasome activity.
- To identify the molecular players involved in this regulatory mechanism.
- To explore potential therapeutic targets for diseases associated with proteasome dysfunction.
Main Methods:
- Utilized Drosophila and human cell lines.
- Identified protein-protein interactions using co-immunoprecipitation and binding assays.
- Assessed proteasome activity and assembly.
- Employed RNA interference (RNAi) and small-molecule inhibitors (XAV939) to modulate tankyrase (TNKS) activity.
Main Results:
- ADP-ribosylation was found to promote 26S proteasome activity in both Drosophila and human cells.
- Tankyrase (TNKS) and 19S assembly chaperones (dp27, dS5b) were identified as direct binding partners of PI31.
- TNKS-mediated ADP-ribosylation of PI31 reduced its affinity for the 20S proteasome, relieving inhibition.
- PI31 modification also promoted 26S assembly by sequestering dp27 and dS5b.
Conclusions:
- ADP-ribosylation by TNKS is a novel mechanism for regulating 26S proteasome assembly and activity.
- Targeting TNKS with inhibitors like XAV939 can modulate proteasome function.
- This regulatory pathway offers potential therapeutic strategies for diseases linked to proteasome dysfunction.
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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...
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...
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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.
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...
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...
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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...
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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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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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02:04Covalently Linked Protein Regulators
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These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.