Related Experiment Video
Updated: Dec 31, 2025
10:27
Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta
Published on: December 5, 2019
9.3K
CRL3s: The BTB-CUL3-RING E3 Ubiquitin Ligases
Pu Wang1, Junbin Song1, Dan Ye2
1Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Advances in Experimental Medicine and Biology
|January 4, 2020
Summary
The CUL3-BTB E3 ligase complexes regulate diverse cellular pathways. This review focuses on CUL3 assembly, substrates, and their role in lung cancer, highlighting future research directions.
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- The ubiquitin proteasome pathway is crucial for eukaryotic cell regulation.
- Cullin-RING ubiquitin ligase (CRL) complexes, particularly CRL3, utilize BTB-adaptor proteins for substrate recognition.
- CUL3-BTB complexes form a significant subset of E3 ubiquitin ligases in mammals.
Purpose of the Study:
- To review recent advancements in CRL3 complex assembly and function.
- To summarize known CRL3 substrates and their biological roles.
- To discuss the implications of CRL3 in human lung cancer and future research avenues.
Main Methods:
- Literature review of recent studies on CRL3 complexes.
- Analysis of CUL3 assembly mechanisms with BTB-containing substrate receptors.
- Examination of CRL3 substrate identification and functional analysis.
Main Results:
- Detailed model for CUL3 assembly with BTB substrate receptors.
- Summary of diverse CRL3 substrates and their functions.
- Discussion of mutual exclusivity of somatic mutations in KEAP1, NRF2, and CUL3 in lung cancer.
Conclusions:
- CRL3 complexes are versatile regulators with diverse substrates.
- Mutations in KEAP1, NRF2, and CUL3 are implicated in human lung cancer.
- Further research is needed to expand the repertoire of CUL3 substrates and understand their roles.
Related Concept Videos
02:58Regulated Protein Degradation
8.6K
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...
8.6K
00:50Anaphase Promoting Complex
3.3K
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...
3.3K
01:13The Proteasome
1.5K
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...
1.5K
02:18The Proteasome
9.9K
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...
9.9K
01:38Intralumenal Vesicles and Multivesicular Bodies
4.6K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
4.6K
01:15Receptor Downregulation in MVBs
2.7K
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...
2.7K