Related Experiment Video
Updated: Dec 8, 2025
12:44
Use of LysoTracker to Detect Programmed Cell Death in Embryos and Differentiating Embryonic Stem Cells
Published on: October 11, 2012
23.8K
The plot thickens: OTULIN regulation in cell death.
Todd Douglas1, Maya Saleh1,2,3
1Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
Molecular & Cellular Oncology
|September 18, 2020
Summary
Post-translational modifications of OTULIN regulate cell death. Hyper-phosphorylation of OTULIN promotes necroptosis, while DUSP14 dephosphorylation limits it.
Area of Science:
- Molecular biology
- Cellular biology
- Biochemistry
Background:
- Post-translational modifications (PTMs) of OTULIN, a deubiquitinase, are crucial for its function in cell death.
- OTULIN's role in regulating necroptosis, a form of programmed cell death, is complex and influenced by its modification state.
Purpose of the Study:
- To investigate how PTMs of OTULIN, specifically phosphorylation, impact its interaction with other proteins and its role in cell death pathways.
- To identify the specific phosphatases that regulate OTULIN phosphorylation and its downstream effects on necroptosis.
Main Methods:
- Western blotting to detect OTULIN phosphorylation.
- Co-immunoprecipitation assays to study protein-protein interactions.
- Cell viability assays to assess necroptosis.
- Genetic manipulation (e.g., siRNA, overexpression) to study the roles of OTULIN, RNF31, CYLD, and DUSP14.
Main Results:
- OTULIN hyper-phosphorylation was found to promote necroptosis.
- This hyper-phosphorylation event sequesters ring finger protein 31 (RNF31, also known as HOIP) away from the cylindromatosis (CYLD) complex.
- The altered complex formation leads to changes in receptor interacting serine/threonine kinase 1 (RIPK1) ubiquitination, favoring necroptosis.
- Dual specificity phosphatase 14 (DUSP14) was identified as a key phosphatase that dephosphorylates OTULIN, thereby limiting necroptosis.
Conclusions:
- OTULIN phosphorylation status is a critical regulator of necroptosis.
- The interplay between OTULIN, RNF31, CYLD, and RIPK1 ubiquitination, modulated by phosphorylation, dictates cell fate.
- DUSP14 acts as a negative regulator of necroptosis by dephosphorylating OTULIN.
Related Concept Videos
01:30Overview of Cell Death
8.8K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
8.8K
01:17The Extrinsic Apoptotic Pathway
7.6K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
7.6K
01:18Autophagic Cell Death
4.0K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.0K
01:30Apoptosis
13.3K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
13.3K
01:31The Intrinsic Apoptotic Pathway
7.8K
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...
7.8K
01:27Molecular Factors Affecting Cell Division
3.7K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.7K