Related Experiment Video
Updated: Aug 7, 2025
09:47
Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
Published on: May 10, 2022
2.6K
E3-ubiquitin ligases and recent progress in osteoimmunology.
Yosuke Asano1, Yoshinori Matsumoto1,2, Jun Wada1
1Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Frontiers in Immunology
|March 13, 2023
Summary
E3-ubiquitin ligases regulate bone and immune functions by degrading proteins. Their dysregulation, as seen in cherubism, highlights their role in craniofacial inflammatory disorders and the osteoimmune system.
Area of Science:
- Biochemistry
- Genetics
- Immunology
Background:
- Ubiquitin-mediated proteasomal degradation is a key post-transcriptional modification involving ubiquitin (Ub), E1, E2, E3 enzymes, deubiquitinating enzymes (DUBs), and the proteasome.
- E3-ubiquitin ligases play critical roles in bone metabolism, immune responses, and inflammation by targeting substrates for degradation.
- Aberrant E3-ubiquitin ligase activity is linked to various human disorders.
Purpose of the Study:
- To review the role of E3-ubiquitin ligases in human disorders.
- To highlight the connection between E3-ubiquitin ligases, the osteoimmune system, and inflammatory craniofacial disorders.
- To summarize recent genetic evidence from human and animal studies.
Main Methods:
- Review of existing literature and genetic studies.
- Analysis of the role of RNF146-mediated degradation of 3BP2 in cherubism.
- Integration of findings from human and animal models.
Main Results:
- Genetic evidence links E3-ubiquitin ligases to bone and immune system regulation.
- Dysregulation of RNF146 and 3BP2 degradation causes cherubism, an inflammatory craniofacial disorder.
- E3-ubiquitin ligases are implicated in the development of disorders related to an abnormal osteoimmune system.
Conclusions:
- E3-ubiquitin ligases are crucial regulators of the osteoimmune system.
- Understanding E3-ubiquitin ligase function is vital for deciphering the pathogenesis of inflammatory craniofacial disorders.
- Targeting E3-ubiquitin ligases may offer therapeutic strategies for related diseases.
Related Concept Videos
02:58Regulated Protein Degradation
7.4K
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...
7.4K
01:15Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
02:04Covalently Linked Protein Regulators
6.9K
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....
6.9K
01:13The Proteasome
920
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...
920
01:24Oligosaccharide Assembly
2.9K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
2.9K
01:20The JAK-STAT Signaling Pathway
9.1K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.1K