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Apaf1 (CED-4 Homolog) Regulates Programmed Cell Death in Mammalian Development
Open accessAbstract
The cytosolic protein APAF1, human homolog of C. elegans CED-4, participates in the CASPASE 9 (CASP9)-dependent activation of CASP3 in the general apoptotic pathway. We have generated by gene trap a null allele of the murine Apaf1. Homozygous mutants die at embryonic day 16.5. Their phenotype includes severe craniofacial malformations, brain overgrowth, persistence of the interdigital webs, and dramatic alterations of the lens and retina. Homozygous embryonic fibroblasts exhibit reduced response to various apoptotic stimuli. In situ immunodetection shows that the absence of Apaf1 protein prevents the activation of Casp3 in vivo. In agreement with the reported function of CED-4 in C. elegans, this phenotype can be correlated with a defect of apoptosis. Our findings suggest that Apaf1 is essential for Casp3 activation in embryonic brain and is a key regulator of developmental programmed cell death in mammals.
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Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990) · Journal of Molecular Biology · doi:10.1006/jmbi.1990.9999 · Cited by 98,669
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Wei, M. C., Zong, W.-X., Cheng, E. H.-Y., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B., & Korsmeyer, S. J. (2001) · Science · doi:10.1126/science.1059108 · Cited by 3,988
Self-citationMammalian Caspases: Structure, Activation, Substrates, and Functions During Apoptosis
Earnshaw, W. C., Martins, L. M., & Kaufmann, S. H. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.383 · Cited by 2,760
Mitochondria and cell death: outer membrane permeabilization and beyond
Tait, S. W. G., & Green, D. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2952 · Cited by 2,593
(2001) · PubMed · Cited by 2,381
Metadata
- Authors
- Cecconi, F., Alvarez-Bolado, G., Meyer, B. I., Roth, K. A., & Gruss, P.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1998-09
- Volume
- 94
- Issue
- 6
- Pages
- 727-737
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2085601531
- Cited by
- 896
- References
- 1
- FWCI
- 28.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Cecconi, F., Alvarez-Bolado, G., Meyer, B. I., Roth, K. A., & Gruss, P. (1998). Apaf1 (CED-4 Homolog) Regulates Programmed Cell Death in Mammalian Development. Cell. https://doi.org/10.1016/s0092-8674(00)81732-8
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
