Mechanisms controlling cellular suicide

Role of Bcl-2 and caspases

R. T. Allen, M. W. Cluck, Devendra K. Agrawal

Research output: Contribution to journalReview article

160 Citations (Scopus)

Abstract

Apoptosis is an essential and highly conserved mode of cell death that is important for normal development, host defense and suppression of oncogenesis. Faulty regulation of apoptosis has been implicated in degenerative conditions, vascular diseases, AIDS and cancer. Among the numerous proteins and genes involved, members of the Bcl-2 family play a central role to inhibit or promote apoptosis. In this article, we present up-to-date information and recent discoveries regarding biochemical functions of Bcl-2 family proteins, positive and negative interactions between these proteins, and their modification and regulation by either proteolytic cleavage or by cytosolic kinases, such as Raf-1 and stress-activated protein kinases. We have critically reviewed the functional role of caspases and the consequences of cleaving key substrates, including lamins, poly(ADP ribose) polymerase and the Rb protein. In addition, we have presented the latest Fas-induced signalling mechanism as a model for receptor-linked caspase regulation. Finally, the structural and functional interactions of Ced-4 and its partial mammalian homologue, apoptosis protease activating faclor-1 (Apaf-1), are presented in a model which includes other Apafs. This model culminates in a caspase/Apaf regulatory cascade to activate the executioners of programmed cell death following cytochrome c release from the mitochondria of mammalian cells. The importance of these pathways in the treatment of disease is highly dependent on further characterization of genes and other regulatory molecules in mammals.

Original languageEnglish
Pages (from-to)427-445
Number of pages19
JournalCellular and Molecular Life Sciences
Volume54
Issue number5
DOIs
StatePublished - 1998

Fingerprint

Caspase 2
Suicide
Caspases
Apoptosis
Cell death
Cell Death
Mitogen-Activated Protein Kinase 8
Lamins
Retinoblastoma Protein
Proteins
Mitochondria
Mammals
Poly(ADP-ribose) Polymerases
Regulator Genes
Cytochromes c
Vascular Diseases
Carcinogenesis
Acquired Immunodeficiency Syndrome
Peptide Hydrolases
Phosphotransferases

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Mechanisms controlling cellular suicide : Role of Bcl-2 and caspases. / Allen, R. T.; Cluck, M. W.; Agrawal, Devendra K.

In: Cellular and Molecular Life Sciences, Vol. 54, No. 5, 1998, p. 427-445.

Research output: Contribution to journalReview article

@article{0af2bd18bc0a4187b841156bb9b08d07,
title = "Mechanisms controlling cellular suicide: Role of Bcl-2 and caspases",
abstract = "Apoptosis is an essential and highly conserved mode of cell death that is important for normal development, host defense and suppression of oncogenesis. Faulty regulation of apoptosis has been implicated in degenerative conditions, vascular diseases, AIDS and cancer. Among the numerous proteins and genes involved, members of the Bcl-2 family play a central role to inhibit or promote apoptosis. In this article, we present up-to-date information and recent discoveries regarding biochemical functions of Bcl-2 family proteins, positive and negative interactions between these proteins, and their modification and regulation by either proteolytic cleavage or by cytosolic kinases, such as Raf-1 and stress-activated protein kinases. We have critically reviewed the functional role of caspases and the consequences of cleaving key substrates, including lamins, poly(ADP ribose) polymerase and the Rb protein. In addition, we have presented the latest Fas-induced signalling mechanism as a model for receptor-linked caspase regulation. Finally, the structural and functional interactions of Ced-4 and its partial mammalian homologue, apoptosis protease activating faclor-1 (Apaf-1), are presented in a model which includes other Apafs. This model culminates in a caspase/Apaf regulatory cascade to activate the executioners of programmed cell death following cytochrome c release from the mitochondria of mammalian cells. The importance of these pathways in the treatment of disease is highly dependent on further characterization of genes and other regulatory molecules in mammals.",
author = "Allen, {R. T.} and Cluck, {M. W.} and Agrawal, {Devendra K.}",
year = "1998",
doi = "10.1007/s000180050171",
language = "English",
volume = "54",
pages = "427--445",
journal = "Cellular and Molecular Life Sciences",
issn = "1420-682X",
publisher = "Birkhauser Verlag Basel",
number = "5",

}

TY - JOUR

T1 - Mechanisms controlling cellular suicide

T2 - Role of Bcl-2 and caspases

AU - Allen, R. T.

AU - Cluck, M. W.

AU - Agrawal, Devendra K.

PY - 1998

Y1 - 1998

N2 - Apoptosis is an essential and highly conserved mode of cell death that is important for normal development, host defense and suppression of oncogenesis. Faulty regulation of apoptosis has been implicated in degenerative conditions, vascular diseases, AIDS and cancer. Among the numerous proteins and genes involved, members of the Bcl-2 family play a central role to inhibit or promote apoptosis. In this article, we present up-to-date information and recent discoveries regarding biochemical functions of Bcl-2 family proteins, positive and negative interactions between these proteins, and their modification and regulation by either proteolytic cleavage or by cytosolic kinases, such as Raf-1 and stress-activated protein kinases. We have critically reviewed the functional role of caspases and the consequences of cleaving key substrates, including lamins, poly(ADP ribose) polymerase and the Rb protein. In addition, we have presented the latest Fas-induced signalling mechanism as a model for receptor-linked caspase regulation. Finally, the structural and functional interactions of Ced-4 and its partial mammalian homologue, apoptosis protease activating faclor-1 (Apaf-1), are presented in a model which includes other Apafs. This model culminates in a caspase/Apaf regulatory cascade to activate the executioners of programmed cell death following cytochrome c release from the mitochondria of mammalian cells. The importance of these pathways in the treatment of disease is highly dependent on further characterization of genes and other regulatory molecules in mammals.

AB - Apoptosis is an essential and highly conserved mode of cell death that is important for normal development, host defense and suppression of oncogenesis. Faulty regulation of apoptosis has been implicated in degenerative conditions, vascular diseases, AIDS and cancer. Among the numerous proteins and genes involved, members of the Bcl-2 family play a central role to inhibit or promote apoptosis. In this article, we present up-to-date information and recent discoveries regarding biochemical functions of Bcl-2 family proteins, positive and negative interactions between these proteins, and their modification and regulation by either proteolytic cleavage or by cytosolic kinases, such as Raf-1 and stress-activated protein kinases. We have critically reviewed the functional role of caspases and the consequences of cleaving key substrates, including lamins, poly(ADP ribose) polymerase and the Rb protein. In addition, we have presented the latest Fas-induced signalling mechanism as a model for receptor-linked caspase regulation. Finally, the structural and functional interactions of Ced-4 and its partial mammalian homologue, apoptosis protease activating faclor-1 (Apaf-1), are presented in a model which includes other Apafs. This model culminates in a caspase/Apaf regulatory cascade to activate the executioners of programmed cell death following cytochrome c release from the mitochondria of mammalian cells. The importance of these pathways in the treatment of disease is highly dependent on further characterization of genes and other regulatory molecules in mammals.

UR - http://www.scopus.com/inward/record.url?scp=0031809920&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031809920&partnerID=8YFLogxK

U2 - 10.1007/s000180050171

DO - 10.1007/s000180050171

M3 - Review article

VL - 54

SP - 427

EP - 445

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

IS - 5

ER -