Gene Symbol: Apaf1
Description: apoptotic peptidase activating factor 1
Alias: apoptotic protease-activating factor 1, apaf-1
Species: rat
Products:     Apaf1

Top Publications

  1. Thompson H, Zhu Z, Jiang W. Identification of the apoptosis activation cascade induced in mammary carcinomas by energy restriction. Cancer Res. 2004;64:1541-5 pubmed
    ..Additional studies revealed that Akt phosphorylation (activation) was reduced in mammary carcinomas from ER rats. Thus, it appears that ER induces apoptosis in mammary carcinomas via a cell survival factor-dependent pathway. ..
  2. Zou H, Henzel W, Liu X, Lutschg A, Wang X. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell. 1997;90:405-13 pubmed
    ..The COOH-terminal region of Apaf-1 comprises multiple WD repeats, which are proposed to mediate protein-protein interactions. Cytochrome c binds to Apaf-1, an event that may trigger the activation of caspase-3, leading to apoptosis. ..
  3. Cecconi F, Alvarez Bolado G, Meyer B, Roth K, Gruss P. Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development. Cell. 1998;94:727-37 pubmed
    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...
  4. Ota K, Yakovlev A, Itaya A, Kameoka M, Tanaka Y, Yoshihara K. Alteration of apoptotic protease-activating factor-1 (APAF-1)-dependent apoptotic pathway during development of rat brain and liver. J Biochem. 2002;131:131-5 pubmed
  5. Potokar M, Kreft M, Chowdhury H, Vardjan N, Zorec R. Subcellular localization of Apaf-1 in apoptotic rat pituitary cells. Am J Physiol Cell Physiol. 2006;290:C672-7 pubmed
  6. Yakovlev A, Ota K, Wang G, Movsesyan V, Bao W, Yoshihara K, et al. Differential expression of apoptotic protease-activating factor-1 and caspase-3 genes and susceptibility to apoptosis during brain development and after traumatic brain injury. J Neurosci. 2001;21:7439-46 pubmed
  7. Song S, Seo H, Lee S, Lee C, Lee J, Yoo K, et al. MicroRNA-17-mediated down-regulation of apoptotic protease activating factor 1 attenuates apoptosome formation and subsequent apoptosis of cardiomyocytes. Biochem Biophys Res Commun. 2015;465:299-304 pubmed publisher
    ..As one of the major components of apoptosomes, apoptotic protease activating factor 1 (Apaf-1) facilitates the formation of apoptosomes containing cytochrome c (Cyto-c) and ..
  8. Li K, Li Y, Shelton J, Richardson J, Spencer E, Chen Z, et al. Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis. Cell. 2000;101:389-99 pubmed
    ..In contrast, cells lacking cytochrome c demonstrate increased sensitivity to cell death signals triggered by TNFalpha. These results define the role of cytochrome c in different apoptotic signaling cascades. ..
  9. Orzáez M, Sancho M, Marchán S, Mondragón L, Montava R, Valero J, et al. Apaf-1 inhibitors protect from unwanted cell death in in vivo models of kidney ischemia and chemotherapy induced ototoxicity. PLoS ONE. 2014;9:e110979 pubmed publisher
    ..Our results provide evidence that Apaf-1 pharmacological inhibition has therapeutic potential for the treatment of apoptosis-related diseases. ..

More Information


  1. Lin H, Liu S, Yen E, Li T, Lai I. microRNA-183 Mediates Protective Postconditioning of the Liver by Repressing Apaf-1. Antioxid Redox Signal. 2017;26:583-597 pubmed publisher
    ..miR-183 mediated the tolerance induced by iPoC in livers via Apaf-1 repressing. Antioxid. Redox Signal. 26, 583-597. ..
  2. Kawamoto Y, Ito H, Ayaki T, Takahashi R. Immunohistochemical localization of apoptosome-related proteins in Lewy bodies in Parkinson's disease and dementia with Lewy bodies. Brain Res. 2014;1571:39-48 pubmed publisher
  3. Siniscalco D, Giordano C, Fuccio C, Luongo L, Ferraraccio F, Rossi F, et al. Involvement of subtype 1 metabotropic glutamate receptors in apoptosis and caspase-7 over-expression in spinal cord of neuropathic rats. Pharmacol Res. 2008;57:223-33 pubmed publisher
  4. Tran T, Andreka P, Rodrigues C, Webster K, Bishopric N. Jun kinase delays caspase-9 activation by interaction with the apoptosome. J Biol Chem. 2007;282:20340-50 pubmed
    ..We propose that this interaction delays formation of the active apoptosome, promoting cell survival during short bursts of oxidative stress. ..
  5. Baker D, Hepple R. Elevated caspase and AIF gene expression correlate with progression of sarcopenia during aging in male F344BN rats. Exp Gerontol. 2006;41:1149-56 pubmed
  6. Choi S, Kim S, Chung K. Huntingtin-interacting protein 1-mediated neuronal cell death occurs through intrinsic apoptotic pathways and mitochondrial alterations. FEBS Lett. 2006;580:5275-82 pubmed
    ..Furthermore, Hip1 could directly bind to Apaf-1, suggesting that the neurotoxic signals of Hip1 transmit through the intrinsic mitochondrial apoptotic pathways and the formation of apoptosome complex. ..
  7. Wright K, Linhoff M, Potts P, Deshmukh M. Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis. J Cell Biol. 2004;167:303-13 pubmed
    ..These data illustrate specifically how the apoptotic pathway acquires increased regulation with cellular differentiation, and are the first to show that IAP function and apoptosome activity are coupled in cells. ..
  8. Razmara M, Srinivasula S, Wang L, Poyet J, Geddes B, DiStefano P, et al. CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis. J Biol Chem. 2002;277:13952-8 pubmed
    ..Overexpression of CARD-8 can also induce apoptosis in transfected cells. The results suggest that CARD-8 represents a new signaling molecule involved in the regulation of caspase-1 and NF-kappaB activation. ..
  9. Yoshida H, Kong Y, Yoshida R, Elia A, Hakem A, Hakem R, et al. Apaf1 is required for mitochondrial pathways of apoptosis and brain development. Cell. 1998;94:739-50 pubmed
    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...
  10. Freathy C, Brown D, Roberts R, Cain K. 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. Hepatology. 2000;32:750-60 pubmed
    ..FMK. These data show that TGF-beta(1) induces apoptosis via release of cytochrome c and activation of the Apaf-1 apoptosome complex, which initiates the caspase cascade. ..
  11. Hao Z, Duncan G, Chang C, Elia A, Fang M, Wakeham A, et al. Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis. Cell. 2005;121:579-591 pubmed publisher
    ..These studies indicate the existence of a Cyt c- and apoptosome-independent but Apaf-1-dependent mechanism(s) for caspase activation. ..
  12. Yuan S, Yu X, Asara J, Heuser J, Ludtke S, Akey C. The holo-apoptosome: activation of procaspase-9 and interactions with caspase-3. Structure. 2011;19:1084-96 pubmed publisher
    ..These binding sites may play a role in pc-3 activation and could allow the formation of hybrid apoptosomes with pc-9 and caspase-3 proteolytic activities. ..
  13. Okouchi M, Okayama N, Aw T. Hyperglycemia potentiates carbonyl stress-induced apoptosis in naïve PC-12 cells: relationship to cellular redox and activator protease factor-1 expression. Curr Neurovasc Res. 2005;2:375-86 pubmed
  14. Li J, Lee B, Lee A. Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53. J Biol Chem. 2006;281:7260-70 pubmed
    ..Our results provide new evidence that, in MEFs, in addition to PUMA, p53 and NOXA are novel components of the ER stress-induced apoptotic pathway, and both contribute to ER stress-induced apoptosis. ..
  15. Bhattacharjee M, Acharya S, Ghosh A, Sarkar P, Chatterjee S, Kumar P, et al. Bax and Bid act in synergy to bring about T11TS-mediated glioma apoptosis via the release of mitochondrial cytochrome c and subsequent caspase activation. Int Immunol. 2008;20:1489-505 pubmed publisher
    ..The present work focuses on the mechanistic approach of how T11TS mediates apoptosis and hence is the first approach of its kind in the field of immunology where the immunotherapeutic molecule's mode of action has been worked out. ..
  16. Henshall D, Bonislawski D, Skradski S, Araki T, Lan J, Schindler C, et al. Formation of the Apaf-1/cytochrome c complex precedes activation of caspase-9 during seizure-induced neuronal death. Cell Death Differ. 2001;8:1169-81 pubmed
    ..These data suggest seizures induce formation of the Apaf-1/cytochrome c complex prior to caspase-9 activation and caspase-9 may be a potential therapeutic target in the treatment of brain injury associated with seizures. ..
  17. Cheung E, Melanson Drapeau L, Cregan S, Vanderluit J, Ferguson K, McIntosh W, et al. Apoptosis-inducing factor is a key factor in neuronal cell death propagated by BAX-dependent and BAX-independent mechanisms. J Neurosci. 2005;25:1324-34 pubmed
    ..Neurons carrying double mutations for Hq/Apaf1-/- (apoptosis proteases-activating factor) are impaired in both caspase-dependent and AIF-mediated mitochondrial ..
  18. Honarpour N, Gilbert S, Lahn B, Wang X, Herz J. Apaf-1 deficiency and neural tube closure defects are found in fog mice. Proc Natl Acad Sci U S A. 2001;98:9683-7 pubmed
    ..Because a complete deficiency in Apaf-1 usually results in perinatal lethality and fog/fog mice more readily survive into adulthood, these mutants serve as a valuable model with which apoptotic cell death can be studied in vivo. ..
  19. Mondragon L, Orzáez M, Sanclimens G, Moure A, Armiñán A, Sepulveda P, et al. Modulation of cellular apoptosis with apoptotic protease-activating factor 1 (Apaf-1) inhibitors. J Med Chem. 2008;51:521-9 pubmed publisher
  20. Xu X, Hua Y, Zhang H, Wu J, Miao Y, Han R, et al. Greater stress protein expression enhanced by combined prostaglandin A1 and lithium in a rat model of focal ischemia. Acta Pharmacol Sin. 2007;28:1097-104 pubmed
    ..Our studies suggest that combined PGA1 and Li may have potential clinical value for the treatment of stroke. ..
  21. Chong Z, Kang J, Maiese K. Apaf-1, Bcl-xL, cytochrome c, and caspase-9 form the critical elements for cerebral vascular protection by erythropoietin. J Cereb Blood Flow Metab. 2003;23:320-30 pubmed
    ..Identification of novel cytoprotective pathways used by EPO may serve as therapeutic targets for cerebral vascular disease. ..
  22. Sakai T, Liu L, Teng X, Mukai Sakai R, Shimada H, Kaji R, et al. Nucling recruits Apaf-1/pro-caspase-9 complex for the induction of stress-induced apoptosis. J Biol Chem. 2004;279:41131-40 pubmed
    ..These findings suggest that Nucling recruits and transports the apoptosome complex during stress-induced apoptosis. ..
  23. Corvaro M, Fuoco C, Wagner M, Cecconi F. Analysis of apoptosome dysregulation in pancreatic cancer and of its role in chemoresistance. Cancer Biol Ther. 2007;6:209-17 pubmed
    ..Its importance during development has been clearly demonstrated by knocking out key genes in mouse. APAF1 is the core protein of the apoptosome and its dosage is also critical in various cancer types, i.e...
  24. Ruiz Vela A, Opferman J, Cheng E, Korsmeyer S. Proapoptotic BAX and BAK control multiple initiator caspases. EMBO Rep. 2005;6:379-85 pubmed
    ..Thus, BAX and BAK confer an essential gateway for the activation of caspases in the intrinsic apoptotic pathway. ..
  25. Mochizuki H, Hayakawa H, Migita M, Shibata M, Tanaka R, Suzuki A, et al. An AAV-derived Apaf-1 dominant negative inhibitor prevents MPTP toxicity as antiapoptotic gene therapy for Parkinson's disease. Proc Natl Acad Sci U S A. 2001;98:10918-23 pubmed
    ..The major mechanism of dopaminergic neuronal death triggered by MPTP seems to be the mitochondrial apoptotic pathway. ..
  26. Yagmurdur H, Ayyildiz A, Karaguzel E, Akgul T, Ustun H, Germiyanoglu C. Propofol reduces nitric oxide-induced apoptosis in testicular ischemia-reperfusion injury by downregulating the expression of inducible nitric oxide synthase. Acta Anaesthesiol Scand. 2008;52:350-7 pubmed publisher
    ..Propofol as an anesthetic agent may attenuate germ cell-specific apoptosis and decrease NO biosynthases through downregulation of iNOS expression in an animal model of testicular torsion and detorsion. ..
  27. Ekshyyan O, Aw T. Decreased susceptibility of differentiated PC12 cells to oxidative challenge: relationship to cellular redox and expression of apoptotic protease activator factor-1. Cell Death Differ. 2005;12:1066-77 pubmed
    ..These results show that nPC12 transition to dPC12 cells afforded protection against oxidative challenge due to maintenance of reduced GSH/GSSG and decreased Apaf-1 expression. ..
  28. Harris B, Franz T, Ullrich S, Cook S, Bronson R, Davisson M. Forebrain overgrowth (fog): a new mutation in the mouse affecting neural tube development. Teratology. 1997;55:231-40 pubmed
  29. Berube C, Boucher L, Ma W, Wakeham A, Salmena L, Hakem R, et al. Apoptosis caused by p53-induced protein with death domain (PIDD) depends on the death adapter protein RAIDD. Proc Natl Acad Sci U S A. 2005;102:14314-20 pubmed
    ..Our findings suggest that caspase-2 contributes to PIDD-mediated cell death, but that it is not the sole effector of this pathway. ..
  30. Zhang Z, Qin X, Tong N, Zhao X, Gong Y, Shi Y, et al. Valproic acid-mediated neuroprotection in retinal ischemia injury via histone deacetylase inhibition and transcriptional activation. Exp Eye Res. 2012;94:98-108 pubmed publisher
    ..Therefore, VPA-mediated neuroprotection against I/R injury in the retina may involve cytoprotective Hsp70 induction via transcriptional activation and inhibition of the mitochondria-mediated apoptosis pathway. ..