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PMID: 9753321 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Apaf1 is required for mitochondrial pathways of apoptosis and brain development.

Cell ·Vol. 94 ·No. 6 ·1998-09-18 ·Pages 739-50

Yoshida H, Kong YY, Yoshida R, Elia AJ, Hakem A, Hakem R, Penninger JM, Mak TW

Abstract

Apoptosis is essential for the precise regulation of cellular homeostasis and development. The role in vivo of Apaf1, a mammalian homolog of C. elegans CED-4, was investigated in gene-targeted Apaf1-/- mice. Apaf1-deficient mice exhibited reduced apoptosis in the brain and striking craniofacial abnormalities with hyperproliferation of neuronal cells. Apaf1-deficient cells were resistant to a variety of apoptotic stimuli, and the processing of Caspases 2, 3, and 8 was impaired. However, both Apaf1-/- thymocytes and activated T lymphocytes were sensitive to Fas-induced killing, showing that Fas-mediated apoptosis in these cells is independent of Apaf1. These data indicate that Apaf1 plays a central role in the common events of mitochondria-dependent apoptosis in most death pathways and that this role is critical for normal development.

MeSH Terms

Animals Apoptosis/physiology Apoptotic Protease-Activating Factor 1 Brain/cytology,embryology Brain Chemistry/physiology Caspase 2 Caspase 3 Caspase 8 Caspase 9 Caspases Cells, Cultured Cysteine Endopeptidases/metabolism Cytochrome c Group/metabolism Embryo, Mammalian/abnormalities Enzyme Precursors/metabolism Fibroblasts/cytology,enzymology Gene Expression Head/abnormalities Membrane Potentials/physiology Mice Mice, Knockout Mitochondria/enzymology Phenotype Proteins/genetics,immunology,metabolism Skin Abnormalities Stem Cells/cytology,metabolism T-Lymphocytes/chemistry,cytology,radiation effects Thymus Gland/chemistry,cytology,radiation effects Ultraviolet Rays fas Receptor/physiology

Chemicals

Apaf1 protein, mouse Apoptotic Protease-Activating Factor 1 Cytochrome c Group Enzyme Precursors Proteins fas Receptor Casp3 protein, mouse Casp8 protein, mouse Casp9 protein, mouse Caspase 2 Caspase 3 Caspase 8 Caspase 9 Caspases Cysteine Endopeptidases

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Yoshida H

The Amgen Institute, Department of Medical Biophysics, University of Toronto, Canada.

Kong Y Y

Yoshida R

Elia A J

Hakem A

Hakem R

Penninger J M

Mak T W

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(00)81733-x

Published

1998-09-18

Pages

739-50

Language

English

Region

United States

NLM ID

0413066

Subset

External Links

PubMed source DOI: 10.1016/s0092-8674(00)81733-x View journal details

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Apaf1 is required for mitochondrial pathways of apoptosis and brain development.

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