Related Experiment Video
Updated: Aug 16, 2026
10:26
Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations
Published on: November 7, 2019
Ubiquitin ligases in malignant lymphoma
Megan S Lim1, Kojo S J Elenitoba-Johnson
1Division of Anatomic Pathology, Department of Pathology, University of Utah, Salt Lake City, Utah 84132, USA. megan.lim@path.utah.edu
Leukemia & Lymphoma
|September 14, 2004
Summary
The ubiquitin-proteasome pathway controls cell functions through protein degradation. E3 ubiquitin ligases are key regulators implicated in malignant lymphoma pathogenesis, offering potential therapeutic targets.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The ubiquitin-proteasome pathway (UPP) is essential for cellular regulation and homeostasis.
- Ubiquitin-dependent proteolysis, mediated by E3 ubiquitin ligases, is a critical post-translational modification.
- E3 ubiquitin ligases play vital roles in cell cycle, signaling, gene transcription, immune response, and differentiation.
Purpose of the Study:
- To highlight the growing number of characterized ubiquitin ligases.
- To identify substrates regulated by E3 ubiquitin ligases.
- To explore the role of E3 ubiquitin ligases in malignant lymphoma pathogenesis.
Main Methods:
- Literature review of recent studies on ubiquitin ligases and their substrates.
- Analysis of implicated proteins in malignant lymphoma.
- Identification of potential research avenues in ubiquitin ligase function.
Main Results:
- E3 ubiquitin ligases regulate the turnover of key proteins including cell cycle regulators (p27Kip1, p21Cip1, p57Kip2, cyclin E), tumor suppressors (p53, RB), signaling kinases (Src, Zap70, PI-3 kinase), apoptosis regulators (Bcl-2, Bax, Bik), and transcription factors (Myc, NF-kappaB, E1F1).
- These regulated proteins are implicated in the pathogenesis of malignant lymphoma.
Conclusions:
- E3 ubiquitin ligases are crucial regulators of cellular processes.
- Dysregulation of E3 ubiquitin ligases and their substrates contributes to malignant lymphoma development.
- Further investigation into the functional role of ubiquitin ligases in malignant lymphoma is warranted.
Related Concept Videos
02:04Covalently Linked Protein Regulators
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.
02:58Regulated Protein Degradation
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...
01:38Intralumenal Vesicles and Multivesicular Bodies
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...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:15Receptor Downregulation in MVBs
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 activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...