Related Experiment Video
Updated: Apr 16, 2026
08:47
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
9.5K
Functional interplay between caspase cleavage and phosphorylation sculpts the apoptotic proteome
Melissa M Dix1, Gabriel M Simon, Chu Wang
1The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Cell
|July 24, 2012
Summary
This study reveals how protein phosphorylation and caspase cleavage pathways crosstalk during apoptosis. Discovering new interactions enhances programmed cell death understanding.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Apoptosis, or programmed cell death, is regulated by caspase proteases that cleave proteins.
- Phosphorylation is also crucial in apoptosis, but its interplay with caspase activity is unclear.
Purpose of the Study:
- To investigate the crosstalk between phosphorylation and caspase proteolysis during apoptosis.
- To map apoptosis-specific phosphorylation events and their relationship to caspase cleavage sites.
Main Methods:
- Utilized a quantitative proteomic platform integrating phosphorylation sites into protein topographical maps.
- Identified and analyzed over 500 apoptosis-specific phosphorylation events.
Main Results:
- Found that apoptosis-specific phosphorylation events are enriched on cleaved proteins and cluster near caspase cleavage sites.
- Demonstrated that caspase cleavage can expose new phosphorylation sites.
- Showed that phosphorylation can directly enhance caspase-8 substrate proteolysis.
Conclusions:
- Revealed significant functional crosstalk between phosphorylation and caspase pathways in apoptosis.
- This crosstalk enhances protein cleavage rates and uncovers new phosphorylation sites.
- Provides a global view of the apoptotic phosphoproteome and its regulation.
Related Concept Videos
01:30Apoptosis
17.2K
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...
17.2K
01:24Caspases
14.7K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
14.7K
01:17The Extrinsic Apoptotic Pathway
9.4K
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...
9.4K
01:31The Intrinsic Apoptotic Pathway
9.3K
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...
9.3K
01:17Phagocytosis of Apoptotic Cells
5.7K
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized...
Normal cells contain receptors that prevent them from being recognized...
5.7K
01:18Autophagic Cell Death
5.1K
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...
5.1K