Book contents
- Frontmatter
- Dedication
- Contents
- List of Contributors
- Preface
- Part 1.1 Analytical techniques: analysis of DNA
- Part 1.2 Analytical techniques: analysis of RNA
- Part 2.1 Molecular pathways underlying carcinogenesis: signal transduction
- Part 2.2 Molecular pathways underlying carcinogenesis: apoptosis
- 30 Apoptosis: the extrinsic pathway
- 31 Apoptosis: the intrinsic pathway
- Part 2.3 Molecular pathways underlying carcinogenesis: nuclear receptors
- Part 2.4 Molecular pathways underlying carcinogenesis: DNA repair
- Part 2.5 Molecular pathways underlying carcinogenesis: cell cycle
- Part 2.6 Molecular pathways underlying carcinogenesis: other pathways
- Part 3.1 Molecular pathology: carcinomas
- Part 3.2 Molecular pathology: cancers of the nervous system
- Part 3.3 Molecular pathology: cancers of the skin
- Part 3.4 Molecular pathology: endocrine cancers
- Part 3.5 Molecular pathology: adult sarcomas
- Part 3.6 Molecular pathology: lymphoma and leukemia
- Part 3.7 Molecular pathology: pediatric solid tumors
- Part 4 Pharmacologic targeting of oncogenic pathways
- Index
- References
30 - Apoptosis: the extrinsic pathway
from Part 2.2 - Molecular pathways underlying carcinogenesis: apoptosis
Published online by Cambridge University Press: 05 February 2015
- Frontmatter
- Dedication
- Contents
- List of Contributors
- Preface
- Part 1.1 Analytical techniques: analysis of DNA
- Part 1.2 Analytical techniques: analysis of RNA
- Part 2.1 Molecular pathways underlying carcinogenesis: signal transduction
- Part 2.2 Molecular pathways underlying carcinogenesis: apoptosis
- 30 Apoptosis: the extrinsic pathway
- 31 Apoptosis: the intrinsic pathway
- Part 2.3 Molecular pathways underlying carcinogenesis: nuclear receptors
- Part 2.4 Molecular pathways underlying carcinogenesis: DNA repair
- Part 2.5 Molecular pathways underlying carcinogenesis: cell cycle
- Part 2.6 Molecular pathways underlying carcinogenesis: other pathways
- Part 3.1 Molecular pathology: carcinomas
- Part 3.2 Molecular pathology: cancers of the nervous system
- Part 3.3 Molecular pathology: cancers of the skin
- Part 3.4 Molecular pathology: endocrine cancers
- Part 3.5 Molecular pathology: adult sarcomas
- Part 3.6 Molecular pathology: lymphoma and leukemia
- Part 3.7 Molecular pathology: pediatric solid tumors
- Part 4 Pharmacologic targeting of oncogenic pathways
- Index
- References
Summary
Introduction
Programmed cell death (also known as PCD) is generally defined as a regulated process by which cells contribute to their own demise. Apoptosis is the best-characterized form of programmed cell death, but alternative non-apoptotic cell-death pathways important in human physiology and disease pathology are now actively studied. Regarding apoptosis, there are two general pathways, the extrinsic pathways and the intrinsic pathways, depending on whether the molecular factor that initiates the death pathway is extra-cellular or intra-cellular. Both extrinsic and intrinsic pathways lead to activation of caspases, the proteases that cleave many key protein targets inside cells, resulting in apoptotic cell morphology and cell death within a few minutes to hours. Although there may be alternative molecular pathways that cause apoptosis-like cell morphology, the term apoptosis most often refers to caspase-dependent cell death.
The extrinsic and intrinsic pathways activate different initiator caspases. Each initiator caspase is activated by a unique complex of proteins. The intrinsic death pathway involves mitochondria and is controlled by pro- and anti-apoptotic Bcl-2-family proteins that facilitate or inhibit the release of cytochrome c from the mitochondrial inter-membrane space. In turn, cytosolic cytochrome c and ATP/ADP bind Apaf-1, inducing oligomerization of Apaf-1 into a heptameric ring structure known as the apoptosome. The apoptosome activates caspase-9, which in turn cleaves and activates caspases-3 and -7 to mediate apoptosis during normal development and to prevent cancer. Other intrinsic apoptotic pathways are initiated by assembly of alternative caspase-activating complexes in response to intra-cellular factors, such as the PIDDosome complex, which activates caspase-2, and the inflammasome, which activates caspase-1 (originally known as ICE, IL-1β-converting enzyme).
- Type
- Chapter
- Information
- Molecular OncologyCauses of Cancer and Targets for Treatment, pp. 353 - 366Publisher: Cambridge University PressPrint publication year: 2013
References
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