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Apoptosis. Molecules and mechanisms
1Department of Molecular Hematology and Therapy, M.D. Anderson Cancer Center, University of Texas, Houston, USA.
Abstract:
This review of the molecules and pathways involved in programmed cell death (apoptosis) discriminates triggers of apoptosis (e.g. chemotherapy, radiation, Fas ligation), modulators of apoptosis (e.g. Bcl-2 family members, Bcl-2 interacting proteins, Apafs, IAPs, and Fas/FasL modulators including FLICE and FLIPs), effectors (caspases 1-13) and cleavage substrates (e.g. PARP). Special consideration is given to the structure-function relationship of Bcl-2 family members and to their post-transcriptional modification. Brief references are made to the role of apoptotic pathway in leukemias and lymphomas and to strategies of modulating apoptotic pathways.
Insights
This review details programmed cell death (apoptosis) pathways, including triggers, modulators like Bcl-2 family proteins, and effectors such as caspases. It explores the structure-function of Bcl-2 family members and their role in cancers.
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- Programmed cell death, or apoptosis, is a fundamental biological process crucial for development and tissue homeostasis.
- Dysregulation of apoptosis is implicated in various diseases, including cancer, autoimmune disorders, and neurodegenerative conditions.
Purpose of the Study:
- To provide a comprehensive review of the molecular machinery governing apoptosis.
- To elucidate the roles of various protein families, such as Bcl-2 and caspases, in regulating cell death.
- To discuss the implications of apoptosis in diseases like leukemia and lymphoma and potential therapeutic strategies.
Main Methods:
- Literature review synthesizing current knowledge on apoptosis.
- Analysis of molecular pathways, including triggers, modulators, and effectors.
- Examination of structure-function relationships, particularly for Bcl-2 family members.
Main Results:
- Detailed classification of apoptosis components: triggers (chemotherapy, radiation, Fas ligation), modulators (Bcl-2 family, IAPs, FLICE, FLIPs), effectors (caspases 1-13), and substrates (PARP).
- Emphasis on the structure-function dynamics of Bcl-2 family members and their post-transcriptional modifications.
- Overview of apoptosis's role in leukemias and lymphomas.
Conclusions:
- Apoptosis is a tightly regulated process involving a complex network of molecules.
- Understanding these pathways, especially the Bcl-2 family, offers therapeutic targets for diseases characterized by aberrant cell death.
- Modulating apoptotic pathways holds promise for treating cancers such as leukemia and lymphoma.