Related Experiment Video
Updated: Jun 22, 2026
05:56
Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
Published on: October 13, 2022
Apoptosis and cancer: mutations within caspase genes
S Ghavami1, M Hashemi, S R Ande
1Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Journal of Medical Genetics
|June 10, 2009
Summary
Dysregulation of programmed cell death, particularly apoptosis, contributes to cancer and chemoresistance. Modulating caspases and their regulators offers promising new anticancer therapies.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- Programmed cell death (apoptosis) is crucial for multicellular organism development and integrity.
- Inactivation of apoptosis can lead to developmental abnormalities, autoimmunity, and cancer.
- Apoptosis deregulation is a key factor in cancer therapy chemoresistance.
Purpose of the Study:
- To review the role of caspases and their natural modulators in apoptosis and cancer.
- To examine studies on caspase gene mutations in tumors.
- To discuss emerging cancer treatments targeting caspases and their regulators.
Main Methods:
- Literature review of programmed cell death mechanisms.
- Analysis of studies screening tumors for mutations in caspase genes and regulators.
- Discussion of experimental anticancer drugs modulating caspase pathways.
Main Results:
- Caspase family proteases are central to apoptosis initiation and execution.
- Natural modulators include IAPs, FLIPs, and Smac/Diablo.
- Emerging treatments involve antagonists for cFLIP, cIAP1, XIAP, and survivin, alongside procaspase-3 activators.
Conclusions:
- Caspase modulation is a viable strategy for cancer therapy.
- Targeting apoptosis pathways presents novel therapeutic opportunities.
- Experimental drugs show potential in overcoming cancer chemoresistance.
Related Concept Videos
01:24Caspases
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 cells.
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...
01:30Apoptosis
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 reduction of the tissue.
01:17The Extrinsic Apoptotic Pathway
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...
01:22Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...