The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Apaf1  -  apoptotic peptidase activating factor 1

Rattus norvegicus

Synonyms: APAF-1, Apoptotic protease-activating factor 1
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Apaf1


High impact information on Apaf1


Biological context of Apaf1


Anatomical context of Apaf1

  • Exogenous EPO maintains both genomic DNA integrity and cellular membrane asymmetry through parallel pathways that prevent the induction of Apaf-1 and preserve mitochondrial membrane potential in conjunction with enhanced Bcl-XL expression [10].
  • We show herein that 2 h after triggering apoptosis with rotenone, Apaf-1 redistributed to the proximity of mitochondria [11].
  • In adult brain, Apaf-1 activity was scarcely detected, while the tissue retained low but significant amounts of procaspase 9 (16% of that in the fetal tissue) and a pro-DEVDase (3.4%) [12].
  • We conclude that (i) c-Jun and Apaf-1 play major roles in the apoptotic cascade of RGC and may represent useful targets for antiapoptotic strategies in RGC in vivo, and (ii) injection of siRNAs into the optic nerve stump is a new method to down-regulate target genes specifically in RGC [13].
  • Furthermore, we found colocalization of activated caspase-3 with apoptotic protease-activating factor-1 (Apaf-1) in apoptotic germ cells, thus indicating the importance of the intrinsic mitochondrial pathway in TGF-beta-induced apoptosis [14].

Associations of Apaf1 with chemical compounds


Regulatory relationships of Apaf1

  • Mitochondria play an important role in the regulation of apoptosis in mammalian cells because apoptotic signals induce mitochondria to release cytochrome c. The latter interacts with Apaf-1 to activate caspase-9, which in turn activates downstream caspase-3 [18].

Other interactions of Apaf1

  • Consistent with the modulation of Apaf-1 and the release of cytochrome c, EPO also inhibits the activation of caspase-9 and caspase-3-like activities [10].
  • These results suggest that differential expression of Apaf-1 and caspase-3 genes may underlie regulation of apoptotic susceptibility during brain development, as well as after acute injury to mature brain, through the intrinsic pathway of caspase activation [1].
  • Normally, caspases exist in cells as inactive pro-enzymes and can be activated by 2 distinct mechanisms: the FADD/caspase 8 cascade, and the Apaf-1/caspase 9 cascade [19].
  • We found that gp120 stimulates p53 activity and induces expression of the p53 pro-apoptotic target Apaf-1 in cultured neurons [17].
  • The E2F-1/p53/Apaf-1 pathway appears to be targeted by UDCA [20].

Analytical, diagnostic and therapeutic context of Apaf1


  1. Differential expression of apoptotic protease-activating factor-1 and caspase-3 genes and susceptibility to apoptosis during brain development and after traumatic brain injury. Yakovlev, A.G., Ota, K., Wang, G., Movsesyan, V., Bao, W.L., Yoshihara, K., Faden, A.I. J. Neurosci. (2001) [Pubmed]
  2. Hyperglycemia potentiates carbonyl stress-induced apoptosis in naïve PC-12 cells: relationship to cellular redox and activator protease factor-1 expression. Okouchi, M., Okayama, N., Aw, T.Y. Current neurovascular research. (2005) [Pubmed]
  3. Cloning and characterization of rat caspase-9: implications for a role in mediating caspase-3 activation and hippocampal cell death after transient cerebral ischemia. Cao, G., Luo, Y., Nagayama, T., Pei, W., Stetler, R.A., Graham, S.H., Chen, J. J. Cereb. Blood Flow Metab. (2002) [Pubmed]
  4. Apaf1 is required for mitochondrial pathways of apoptosis and brain development. Yoshida, H., Kong, Y.Y., Yoshida, R., Elia, A.J., Hakem, A., Hakem, R., Penninger, J.M., Mak, T.W. Cell (1998) [Pubmed]
  5. Transforming growth factor-beta(1) induces apoptosis in rat FaO hepatoma cells via cytochrome c release and oligomerization of Apaf-1 to form a approximately 700-kd apoptosome caspase-processing complex. Freathy, C., Brown, D.G., Roberts, R.A., Cain, K. Hepatology (2000) [Pubmed]
  6. Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury. Springer, J.E., Azbill, R.D., Knapp, P.E. Nat. Med. (1999) [Pubmed]
  7. Apaf-1 deficiency and neural tube closure defects are found in fog mice. Honarpour, N., Gilbert, S.L., Lahn, B.T., Wang, X., Herz, J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  8. Decreased susceptibility of differentiated PC12 cells to oxidative challenge: relationship to cellular redox and expression of apoptotic protease activator factor-1. Ekshyyan, O., Aw, T.Y. Cell Death Differ. (2005) [Pubmed]
  9. Formation of the Apaf-1/cytochrome c complex precedes activation of caspase-9 during seizure-induced neuronal death. Henshall, D.C., Bonislawski, D.P., Skradski, S.L., Araki, T., Lan, J.Q., Schindler, C.K., Meller, R., Simon, R.P. Cell Death Differ. (2001) [Pubmed]
  10. Apaf-1, Bcl-xL, cytochrome c, and caspase-9 form the critical elements for cerebral vascular protection by erythropoietin. Chong, Z.Z., Kang, J.Q., Maiese, K. J. Cereb. Blood Flow Metab. (2003) [Pubmed]
  11. Subcellular localization of Apaf-1 in apoptotic rat pituitary cells. Potokar, M., Kreft, M., Chowdhury, H.H., Vardjan, N., Zorec, R. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  12. Alteration of apoptotic protease-activating factor-1 (APAF-1)-dependent apoptotic pathway during development of rat brain and liver. Ota, K., Yakovlev, A.G., Itaya, A., Kameoka, M., Tanaka, Y., Yoshihara, K. J. Biochem. (2002) [Pubmed]
  13. Down-regulation of apoptosis mediators by RNAi inhibits axotomy-induced retinal ganglion cell death in vivo. Lingor, P., Koeberle, P., Kügler, S., Bähr, M. Brain (2005) [Pubmed]
  14. Effects of TGF-betas and a specific antagonist on apoptosis of immature rat male germ cells in vitro. Konrad, L., Keilani, M.M., Laible, L., Nottelmann, U., Hofmann, R. Apoptosis (2006) [Pubmed]
  15. Taurine inhibits apoptosis by preventing formation of the Apaf-1/caspase-9 apoptosome. Takatani, T., Takahashi, K., Uozumi, Y., Shikata, E., Yamamoto, Y., Ito, T., Matsuda, T., Schaffer, S.W., Fujio, Y., Azuma, J. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  16. Gene expression analysis of the rat testis after treatment with di(2-ethylhexyl) phthalate using cDNA microarray and real-time RT-PCR. Kijima, K., Toyosawa, K., Yasuba, M., Matsuoka, N., Adachi, T., Komiyama, M., Mori, C. Toxicol. Appl. Pharmacol. (2004) [Pubmed]
  17. Regulation of neuronal P53 activity by CXCR 4. Khan, M.Z., Shimizu, S., Patel, J.P., Nelson, A., Le, M.T., Mullen-Przeworski, A., Brandimarti, R., Fatatis, A., Meucci, O. Mol. Cell. Neurosci. (2005) [Pubmed]
  18. Polyamine depletion prevents camptothecin-induced apoptosis by inhibiting the release of cytochrome c. Yuan, Q., Ray, R.M., Johnson, L.R. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  19. RNA expression bcl-w, a new related protein Bcl-2 family, and caspase-3 in isolated sertoli cells from pre-pubertal rat testes. Giannattasio, A., Angeletti, G., De Rosa, M., Zarrilli, S., Ambrosino, M., Cimmino, A., Coppola, C., Panza, G., Calafiore, R., Colao, A., Abete, O., Lombardi, G. J. Endocrinol. Invest. (2002) [Pubmed]
  20. A distinct microarray gene expression profile in primary rat hepatocytes incubated with ursodeoxycholic acid. Castro, R.E., Solá, S., Ma, X., Ramalho, R.M., Kren, B.T., Steer, C.J., Rodrigues, C.M. J. Hepatol. (2005) [Pubmed]
  21. Reduction of caspase-8 and -9 cleavage is associated with increased c-FLIP and increased binding of Apaf-1 and Hsp70 after neonatal hypoxic/ischemic injury in mice overexpressing Hsp70. Matsumori, Y., Northington, F.J., Hong, S.M., Kayama, T., Sheldon, R.A., Vexler, Z.S., Ferriero, D.M., Weinstein, P.R., Liu, J. Stroke (2006) [Pubmed]
WikiGenes - Universities