Related Experiment Video
Updated: May 27, 2025
11:36
In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
10.6K
The Ubiquitin Code in Disease Pathogenesis and Progression: Composition, Characteristics and its Potential as a
Ji Su Lee1,2, Hye Yeon Kim1,2, Yong Tae Kwon1,2,3,4
1Cellular Degradation Biology Center, Seoul National University, 03080 Seoul, Republic of Korea.
Discovery Medicine
|February 20, 2025
Summary
Ubiquitin (Ub) conjugation regulates protein degradation. Diverse Ub chains, formed through various lysine linkages, control cellular functions and disease progression, offering therapeutic targets like targeted protein degradation (TPD).
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Ubiquitin (Ub) conjugation is a key post-translational modification.
- It plays a crucial role in protein degradation and cellular signaling.
- The process involves ubiquitin-activating (E1), ubiquitin-conjugating (E2), and ubiquitin ligases (E3) enzymes.
Purpose of the Study:
- To provide an overview of the ubiquitin code.
- To highlight the linkage-specific roles of ubiquitin chains in biological processes.
- To discuss the therapeutic potential of modulating the ubiquitin code.
Main Methods:
- Review of existing literature on ubiquitination.
- Analysis of ubiquitin chain linkage types and their functional consequences.
- Exploration of disease pathogenesis and therapeutic strategies related to ubiquitination.
Main Results:
- Ubiquitination involves conjugation of Ub to substrates and subsequent Ub polymerization.
- Seven lysine residues and the N-terminal methionine of Ub can form diverse chain linkages.
- These linkages (homotypic, mixed, branched) elicit distinct cellular responses.
Conclusions:
- The ubiquitin code, through diverse linkage types, regulates critical cellular functions.
- Dysregulation of the ubiquitin code is implicated in cancer, neurodegeneration, and immune disorders.
- Targeting the ubiquitin code, including via targeted protein degradation (TPD), presents promising therapeutic avenues.
Related Concept Videos
01:13The Proteasome
801
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...
801
02:58Regulated Protein Degradation
7.1K
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...
7.1K
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
01:23Regulation of Expression at Multiple Steps
864
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...
864
03:03mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
01:15Receptor Downregulation in MVBs
2.0K
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...
2.0K