Limits...
Cell differentiation: reciprocal regulation of Apaf-1 and the inhibitor of apoptosis proteins.

Lindholm D, Arumäe U - J. Cell Biol. (2004)

Bottom Line: The molecular mechanisms by which differentiated cells combat cell death and injury have remained unclear.In the current issue, it has been shown in neurons that cell differentiation is accompanied by a decrease in Apaf-1 and the activity of the apoptosome with an increased ability of the inhibitor of apoptosis proteins (IAPs) to sustain survival (Wright et al., 2004).These results, together with earlier ones, deepen our understanding of how cell death and the apoptosome are regulated during differentiation and in tumor cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Uppsala University, Biomedical Centre, S-751 23 Uppsala, Sweden. Dan.Lindholm@neuro.uu.se

ABSTRACT
The molecular mechanisms by which differentiated cells combat cell death and injury have remained unclear. In the current issue, it has been shown in neurons that cell differentiation is accompanied by a decrease in Apaf-1 and the activity of the apoptosome with an increased ability of the inhibitor of apoptosis proteins (IAPs) to sustain survival (Wright et al., 2004). These results, together with earlier ones, deepen our understanding of how cell death and the apoptosome are regulated during differentiation and in tumor cells.

Show MeSH

Related in: MedlinePlus

The apoptosome death wheel. Apaf-1 together with procaspase-9 form the wheel-shaped apoptosome complex. Cytochrome c binds to Apaf-1 and drives cell death through the activation of caspase 3. The IAPs, such as XIAP, can counteract caspase activation, but this brake on cell death is diminished by Smac/Diablo released from the mitochondria. The steady-state levels of the various interacting proteins may vary between cell types and with cell differentiation. As well as the apoptosome, other cellular pathways can be activated and probably interact during cell demise.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2172544&req=5

fig1: The apoptosome death wheel. Apaf-1 together with procaspase-9 form the wheel-shaped apoptosome complex. Cytochrome c binds to Apaf-1 and drives cell death through the activation of caspase 3. The IAPs, such as XIAP, can counteract caspase activation, but this brake on cell death is diminished by Smac/Diablo released from the mitochondria. The steady-state levels of the various interacting proteins may vary between cell types and with cell differentiation. As well as the apoptosome, other cellular pathways can be activated and probably interact during cell demise.

Mentions: Proteins of the Bcl-2 family are major determinants of cell viability, controlling the mitochondrial membrane pore formation induced by different death signals converging on the organelle (Danial and Korsmeyer, 2004). Following an increase in the permeability of the outer membrane, cytochrome c and other pro-apoptotic proteins are released from the intermembrane space triggering cell demise (Lindholm et al., 2004). In the cytosol, a complex known as the apoptosome is formed from apoptotic protease activating factor-1 (Apaf-1), procaspase-9, and cytochrome c/dATP. Apaf-1 resembles the C. elegans protein CED-4 that is required for apoptosis in the worm (Li et al., 1997; Zhou et al., 1997). Apaf-1 has a caspase recruitment domain (CARD) that allows it to bind to the CARD in caspase 9, a central P loop motif that binds ATP, and at the COOH terminus are WD40 repeats that bind to cytochrome c (Fig. 1). Oligomerization of Apaf-1 leads to autoactivation of procaspase-9 that in turn cleaves caspase-3, ultimately causing cell death (Acehan et al., 2002; Hill et al., 2004). The structure of the apoptosome thus constitutes a cellular “death wheel” (Fig. 1).


Cell differentiation: reciprocal regulation of Apaf-1 and the inhibitor of apoptosis proteins.

Lindholm D, Arumäe U - J. Cell Biol. (2004)

The apoptosome death wheel. Apaf-1 together with procaspase-9 form the wheel-shaped apoptosome complex. Cytochrome c binds to Apaf-1 and drives cell death through the activation of caspase 3. The IAPs, such as XIAP, can counteract caspase activation, but this brake on cell death is diminished by Smac/Diablo released from the mitochondria. The steady-state levels of the various interacting proteins may vary between cell types and with cell differentiation. As well as the apoptosome, other cellular pathways can be activated and probably interact during cell demise.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172544&req=5

fig1: The apoptosome death wheel. Apaf-1 together with procaspase-9 form the wheel-shaped apoptosome complex. Cytochrome c binds to Apaf-1 and drives cell death through the activation of caspase 3. The IAPs, such as XIAP, can counteract caspase activation, but this brake on cell death is diminished by Smac/Diablo released from the mitochondria. The steady-state levels of the various interacting proteins may vary between cell types and with cell differentiation. As well as the apoptosome, other cellular pathways can be activated and probably interact during cell demise.
Mentions: Proteins of the Bcl-2 family are major determinants of cell viability, controlling the mitochondrial membrane pore formation induced by different death signals converging on the organelle (Danial and Korsmeyer, 2004). Following an increase in the permeability of the outer membrane, cytochrome c and other pro-apoptotic proteins are released from the intermembrane space triggering cell demise (Lindholm et al., 2004). In the cytosol, a complex known as the apoptosome is formed from apoptotic protease activating factor-1 (Apaf-1), procaspase-9, and cytochrome c/dATP. Apaf-1 resembles the C. elegans protein CED-4 that is required for apoptosis in the worm (Li et al., 1997; Zhou et al., 1997). Apaf-1 has a caspase recruitment domain (CARD) that allows it to bind to the CARD in caspase 9, a central P loop motif that binds ATP, and at the COOH terminus are WD40 repeats that bind to cytochrome c (Fig. 1). Oligomerization of Apaf-1 leads to autoactivation of procaspase-9 that in turn cleaves caspase-3, ultimately causing cell death (Acehan et al., 2002; Hill et al., 2004). The structure of the apoptosome thus constitutes a cellular “death wheel” (Fig. 1).

Bottom Line: The molecular mechanisms by which differentiated cells combat cell death and injury have remained unclear.In the current issue, it has been shown in neurons that cell differentiation is accompanied by a decrease in Apaf-1 and the activity of the apoptosome with an increased ability of the inhibitor of apoptosis proteins (IAPs) to sustain survival (Wright et al., 2004).These results, together with earlier ones, deepen our understanding of how cell death and the apoptosome are regulated during differentiation and in tumor cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Uppsala University, Biomedical Centre, S-751 23 Uppsala, Sweden. Dan.Lindholm@neuro.uu.se

ABSTRACT
The molecular mechanisms by which differentiated cells combat cell death and injury have remained unclear. In the current issue, it has been shown in neurons that cell differentiation is accompanied by a decrease in Apaf-1 and the activity of the apoptosome with an increased ability of the inhibitor of apoptosis proteins (IAPs) to sustain survival (Wright et al., 2004). These results, together with earlier ones, deepen our understanding of how cell death and the apoptosome are regulated during differentiation and in tumor cells.

Show MeSH
Related in: MedlinePlus