Related Experiment Video
Updated: Jun 26, 2025
09:00
Detection of Protein Ubiquitination
Published on: August 19, 2009
42.9K
Pin1-Catalyzed Conformation Changes Regulate Protein Ubiquitination and Degradation
Jessica Jeong1,2, Muhammad Usman1,2, Yitong Li1,2
1Departments of Biochemistry and Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada.
Cells
|May 10, 2024
Summary
The prolyl isomerase Pin1 regulates protein stability through ubiquitination, impacting cancer and neurodegenerative diseases. Targeting this pathway offers novel therapeutic strategies for these conditions.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Biology
Background:
- Prolyl isomerase Pin1 catalyzes cis-trans conformational changes of phosphorylated Ser/Thr-Pro motifs.
- Pin1 regulates protein substrate affinity for E3 ubiquitin ligases, modulating protein turnover.
- Pin1's role is critical in both physiological processes and disease states.
Purpose of the Study:
- To review recent advancements in Pin1-regulated ubiquitination.
- To highlight Pin1's role in cancer and neurodegenerative diseases.
- To propose a novel therapeutic approach targeting the ubiquitin-proteasome system.
Main Methods:
- Literature review of recent advancements in Pin1 research.
- Analysis of Pin1's role in cancer progression and neurodegeneration.
- Exploration of therapeutic strategies involving the ubiquitin-proteasome system.
Main Results:
- Pin1 promotes cancer by stabilizing oncoproteins and destabilizing tumor suppressors.
- Pin1 regulates protein turnover in neurodegenerative disorders.
- A novel therapeutic approach using antibody-mediated degradation of targets is proposed.
Conclusions:
- Pin1 is a key regulator of protein turnover implicated in cancer and neurodegenerative diseases.
- Targeting Pin1-regulated ubiquitination presents therapeutic opportunities.
- Leveraging the ubiquitin-proteasome system with antibodies offers a novel treatment strategy.
Related Concept Videos
02:58Regulated Protein Degradation
7.2K
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...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.2K
02:04Covalently Linked Protein Regulators
6.8K
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.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
01:13The Proteasome
830
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...
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...
830
01:23Regulation of Expression at Multiple Steps
893
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...
893
01:37The Unfolded Protein Response
4.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.6K
01:17The Proteasome Structure
747
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...
The proteasome is an...
747