Scientific background: |
Apoptotic peptidase activating factor 1, also known as APAF1, is a protein which in humans is encoded by the APAF1 gene. This gene is mapped to chromosome 12q23. It encodes a cytoplasmic protein that initiates apoptosis. And it is an essential downstream effector of p53-mediated apoptosis. This protein contains several copies of the WD40 repeat domain, a caspase recruitment domain (CARD), and an ATPase domain (NB-ARC). In the presence of cytochrome c and dATP, APAF1 assembles into an oligomeric apoptosome, which is responsible for activation of procaspase-9 and maintenance of the enzymatic activity of processed caspase-9. Furthermore, APAF1 is inactivated in metastatic melanomas, leading to defects in the execution of apoptotic cell death. Additionally, APAF1 has been shown to interact with NLRP1, Caspase-9, APIP, BCL2-like 1 and HSPA4. |
References: |
1. Kim, H.; Jung, Y. K.; Kwon, Y. K.; Park, S. H. : Assignment of apoptotic protease activating factor-1 gene (APAF1) to human chromosome band 12q23 by fluorescence in situ hybridization. Cytogenet. Cell Genet. 87: 252-253, 1999.
2. Robles, A. I.; Bemmels, N. A.; Foraker, A. B.; Harris, C. C. : APAF-1 is a transcriptional target of p53 in DNA damage-induced apoptosis. Cancer Res. 61: 6660-6664, 2001.
3. Bao, Q.; Lu, W.; Rabinowitz, J. D.; Shi, Y. : Calcium blocks formation of apoptosome by preventing nucleotide exchange in Apaf-1. Molec. Cell 25: 181-192, 2007.
4. Soengas, M. S.; Capodieci, P.; Polsky, D.; Mora, J.; Esteller, M.; Opitz-Araya, X.; McCombie, R.; Herman, J. G.; Gerald, W. L.; Lazebnik, Y. A.; Cordon-Cardo, C.; Lowe, S. W. : Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. Nature 409: 207-211, 2001.
5. Chu, Z L; Pio F, Xie Z, Welsh K, Krajewska M, Krajewski S, Godzik A, Reed J C (Mar. 2001). "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". J. Biol. Chem. (United States) 276 (12): 9239-45.
6. Cho, Dong-Hyung; Hong Yeon-Mi, Lee Ho-June, Woo Ha-Na, Pyo Jong-Ok, Mak Tak W, Jung Yong-Keun (Sep. 2004). "Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein". J. Biol. Chem. (United States) 279 (38): 39942-50.
7. Li, P; Nijhawan D, Budihardjo I, Srinivasula S M, Ahmad M, Alnemri E S, Wang X (Nov. 1997). "Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade". Cell (UNITED STATES) 91 (4): 479-89. |