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APAF1 (Apoptotic protease activating factor 1)

Identity

Other namesKIAA0413
Apaf-1
HGNC (Hugo) APAF1
LocusID (NCBI) 317
Location 12q23.1
Location_base_pair Starts at 99039078 and ends at 99129211 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order
  • solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 3 12q23
  • IKK interacting protein 12q23.1
  • APAF1 12q23
  • E2a-Pbx1-associated protein / EB1 12q23.1-q23.2
  • DNA/RNA

    Description The APAF1 gene is comprised of 27 exons, with the coding region spanning 26 exons (the ATG is in the second exon
    Transcription Five isoforms of APAF1 cDNA have been identified in Homo sapiens
  • the original APAF1 (also called Apaf-1S) is 3585 bp long (it contains 12 WD40 repeats);
  • the APAF1-1M isoform (3618 bp) contains an insertion of 33 nt after position 295 of the first published sequence (11 aa insertion GKDSVSGITSY between aa 98 and 99; it also contains 12 WD40 repeats);
  • the APAF1XS isoform (3516 bp) contains the same insertion of Apaf-1M form, lacks the base pairs from 3171 to 3296 of the Apaf-1S form (the deletion is in WD40 domain) but has an insertion of 24 nt at position 1725
  • the APAF1L (3714 bp) contains an insertion of 129 nt at position 2466(contains 13 WD40 repeats);
  • the APAF1XL (3747 bp)isoform contains the same insertion of APAF1M form, plus and additional insertion of 129 bp (43 aa beetween aa 811-812; Apaf-1XL also contains 13 WD40 repeats);
  • Pseudogene not known

    Protein

     
      Figure 1: The conformational changes in the APAF1 molecules lead to apoptosome formation and to the activation of apoptosis. However, the assembly and the functioning of the apoptosome is regulated by mithocondrial and cytosolic factors (modif. from E. Ferraro et al. 2004)
    Description the protein can be divided into three domains: the N-terminal is a CARD domain and is necessary for APAF1 function; alternatively, it can bind the WD40 domain or cytochrome C. The ced-4-like domain is responsible for APAF1 conformational changes. The C-terminal WD40 domain is a negative regulator element composed of 12 or 13 WD40 repeats: it can bind the CARD domain but it can probably interact with other apoptotic regulator proteins as well.
    Expression APAF1 Promoter can interact with E2F1 (also E2F2-3) and p53 which can in turn regulate its expression.
    Localisation cytosolic
    Function APAF1 is the structural core of the apoptosome. When the mitochondrial pathway of apoptosis is activated, cytochrome c is released from mitochondria to cytosol, and then binds to APAF1 CARD domain changing its conformation. A further binding of ATP molecules mediates a second conformational change which leads to open APAF1 conformation. By means of the CARD domain, seven APAF1 molecules bind to each other and to seven molecules of initiator Caspase-9 forming the apoptosome and causing the activation of effector caspases. The formation of apoptosome and the activation of caspases are regulated by numerous interacting proteins.
    Homology CED-4 (C. elegans); DARK (D. melanogaster); CARD proteins.

    Mutations

    Germinal not known in H. sapiens.
    Somatic not known in H. sapiens.

    Implicated in

    Entity Skin Cancers ( Melanoma, Basal Cell Carcinoma, Squamous Cell Carcinoma).
    Cytogenetics Frequent LOH in 12q22-23 locus (primary melanomas: 20-25% metastatic melanomas 35-40%).
    Oncogenesis The silencing of Apaf1 expression is often found in Melanomas. Two main mechanisms have been posited for APAF1 dimininution, either the allelic LOH in 12q22-23 locus and/or a transcriptional silencing by promoter methylation. The inactivation was not found in Nevi but it increased significantly in the later stages of carcinogenesis, when primary melanomas are fully developed (1-3mm of diameter). Very often such inactivation was associated with metastatic melanomas. Moreover, the APAF1 level is correlated with chemosensivity to different agents; different studies demonstrate that overexpressing or restoring a normal APAF1 level could sensitize chemoresistant melanoma cell lines, in vitro. Recently, APAF1 LOH determination on blood serum DNA has been proposed as a marker for selecting appropriate chemotherapy in stage IV melanoma patients.
      
    Entity Brain tumors (neural tumors, glial tumors)
    Cytogenetics Frequent LOH in 12q22-23 locus in glioblastomas (40%)
    Oncogenesis APAF1 seems to be downregulated or absent in Glioblastomas at mRNA and protein level. In addition, the co-overexpression of APAF1 and Caspase-9 sensitizes glioma cell lines (U-251 and U-373 MG) to p53-dependent apoptosis. Other modulations of the apoptosome-related apoptosis have been successfully conducted in order to induce apoptosis in glioma resistant lines. By contrast, APAF1 seems to be active in Neuroblastomas while there are no studies about a putative APAF1 role in other glial tumors (such as ependimoma, astrocytoma, ganglioglioma).
      
    Entity Head and neck cancers and odontogenic tumors.
    Oncogenesis There is no direct evidence of APAF1's role in the oncogenesis of these types of cancer even though Apaf1 loss has been correlated with gain of Cisplatin Chemoresistance in HSC-2CR cells (derived from HSC-2 head squamous carcinoma cells).
      
    Entity Gastro-intestinal tract cancers ( oesophagus cancer, gastric cancer, gallbladder cancer, ampulla of vater cancer, peritoneum cancer, vermiform appendix cancer, colon cancer, rectal cancer, cancer of the anus).
    Oncogenesis A low frequency of mutations (10-15 % of cases) is found in ColoRectal and Gastric Cancer. these mutations are due to the genetics of microsatellite instability and appear to be heterozygous. No evidences of APAF1 involvement have been found in the pathogenesis of the other tumors mentioned
      
    Entity Exocrinus pancreas cancers (various stages of the pancreas ductal adenocarcinoma - PDAC)
    Cytogenetics 12q 1ocus deletions could be considered among the most frequent deletions in PDAC.
    Oncogenesis There is no direct evidence of APAF1 mutations in the progression of the PDAC (some even deny its possible role completely). There are many studies, however, which point out the 12q22-23 locus LOH or mutation in PDAC. Most of the mutated genes involved (such as K-Ras, p53, p16INK4a, p19ARF) can control the APAF1 level directly or indirectly throught the action of p53 and E2F-1 which both have active binding boxes to the APAF1 promoter.
      
    Entity Liver cancer and liver metastases
    Oncogenesis Methylation is a common feature in hepatocellular carcinoma (HCC) regulation. While the analysis of promoters methylation in HCC samples showed that the APAF1 gene is not hypermethylated, the HepG2 cells exposed to a demethylating agent (DEM, diethyl maleate) showed an increased level of Apaf1 and of some caspases which lead to G2 phase arrest and apoptosis.
      
    Entity Lung cancer
    Oncogenesis There is no direct evidence for abrogation of APAF1 function in lung cancer. However, the APAF1/Caspase-9 upregulation seem to be a protective mechanism in some NSCLC ( non small cell lung carcinoma) cell lines, while in other NSCLC lines (such as the NCI-H460) an indirect APAF1 loss of function is mediated by the upregulation of XIAP (an inhibitor of Apoptosome assembly). Furthermore, a driven expression of APAF1/ Caspase-9 (through the Inibition of XIAP in NCI-H460 cells or with low dose lung cancer cell lines) seems to augment sensitivity to death.
      
    Entity Tumors of the female reproductive organs ( ovarian carcinoma, neoplasms of Fallopian tube, endometrium, cervix, vulva and vagina)
    Oncogenesis In ovarian carcinoma, the APAF1 gene seems to be active. However, dysfunction in the apoptosome assembly process has been correlated with chemoresistance. In contrast, loss of heterozygosity was found in the apaf1 locus in malignant ovarian germ cell tumors. There is no information about the reproductive tract.
      
    Entity Tumors of the male reproductive organs ( seminoma, nonseminomatous germ cell tumors, sex cord-stromal tumors , other testis cancers, neoplasms of prostate, tumor of the penis)
    Cytogenetics Frequent deletions in Chromosome 12 long and short arm in germ line tumors; LOH in 12q22-23 is present in seminomas, non-seminomatous tumors and in mixed teratomas with various reported percentage (20-45%)
    Oncogenesis In Germ line tumors the APAF1 locus is often deleted; however it seems that APAF1 level was normal in various analyzed lines. Interestingly, Cisplatin treatment of a embryonal carcinoma cell line, TTSC-3 lead to the differentiation of the carcinoma through the up-regulation of pro-differentiation and pro-apoptotic genes (such as APAF1, Caspase-8 and TNFR1). In Prostatic Tumor there is no evidence of APAF1 involvement; however some studies have been conducted demontrating an increase of Apaf1 at transcription level as a cellular response to chemotherapeutic agents.
      
    Entity Urinary tract tumors ( renal cell carcinoma, neoplasms of the renal pelvis, ureter, bladder, urethra)
    Oncogenesis The Apoptosome function seems to be active in primary samples and in a few cell lines of Renal Cell Carcinoma. There are no informations about the urinary tract.
      
    Entity Hematopoietic system tumors.
    Oncogenesis It's not clear if APAF1 gene is corrupted in Leukaemias and Lymphomas. However, while the methylation of the promoter was demonstrated in different kinds of leukaemia, the protein level does not correlate with the messenger level, suggesting a multistep regulation in APAF1 expression. Furthermore, it has been demonstrated that the APAF1 overexpression, conducted by in vitro transfection or by chemoadiuvants, could overcome the resistance to chemo-radiotherapeutic agents.
      
    Entity Bone and soft tissue cancers (osteoma, sarcoma, fibroma, osteosarcoma)
    Oncogenesis There is no direct evidence of APAF1 role in the oncogenesis of these types of cancer even though in Ewing's sarcoma cell lines the Apaf1 low level found in two different lines (STA-ET-2.1 and STA-ET-2.2) was correlated with chemoresistance to p53-dependent death stimuli compared with lines with normal APAF1 level. APAF1 was also absent and correlated with chemoresistance in the HT-1080 fibrosacroma cell line.
      
    Entity Various tumors ( eye tumor, heart and great vessels tumors, neoplasm of the endocrine glands and of the diffuse endocrine system, tumor of mesotheliums)
    Oncogenesis At present, there is no direct evidence of APAF1 involvement in the carcinogenesis of these neoplasms.
      

    External links

    Nomenclature
    HGNC (Hugo)APAF1   576
    Cards
    AtlasAPAF1ID422
    Entrez_Gene (NCBI)APAF1  317  apoptotic peptidase activating factor 1
    GeneCards (Weizmann)APAF1
    Ensembl (Hinxton)ENSG00000120868 [Gene_View]  chr12:99039078-99129211 [Contig_View]  APAF1 [Vega]
    ICGC DataPortalENSG00000120868
    AceView (NCBI)APAF1
    Genatlas (Paris)APAF1
    WikiGenes317
    SOURCE (Princeton)NM_001160 NM_013229 NM_181861 NM_181868 NM_181869
    Genomic and cartography
    GoldenPath (UCSC)APAF1  -  12q23.1   chr12:99039078-99129211 +  12q23   [Description]    (hg19-Feb_2009)
    EnsemblAPAF1 - 12q23 [CytoView]
    Mapping of homologs : NCBIAPAF1 [Mapview]
    OMIM602233   
    Gene and transcription
    Genbank (Entrez)AB007873 AB103079 AF013263 AF134397 AF149794
    RefSeq transcript (Entrez)NM_001160 NM_013229 NM_181861 NM_181868 NM_181869
    RefSeq genomic (Entrez)AC_000144 NC_000012 NC_018923 NG_029094 NT_029419 NW_001838061 NW_004929384
    Consensus coding sequences : CCDS (NCBI)APAF1
    Cluster EST : UnigeneHs.552567 [ NCBI ]
    CGAP (NCI)Hs.552567
    Alternative Splicing : Fast-db (Paris)GSHG0006927
    Alternative Splicing GalleryENSG00000120868
    Gene ExpressionAPAF1 [ NCBI-GEO ]     APAF1 [ SEEK ]   APAF1 [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtO14727 (Uniprot)
    NextProtO14727  [Medical]
    With graphics : InterProO14727
    Splice isoforms : SwissVarO14727 (Swissvar)
    Domaine pattern : Prosite (Expaxy)CARD (PS50209)    WD_REPEATS_1 (PS00678)    WD_REPEATS_2 (PS50082)    WD_REPEATS_REGION (PS50294)   
    Domains : Interpro (EBI)Apoptotic_pept-activating_1    CARD    DEATH-like_dom    Disease_R    G-protein_beta_WD-40_rep    NB-ARC    P-loop_NTPase    WD40/YVTN_repeat-like_dom    WD40_repeat    WD40_repeat_CS    WD40_repeat_dom   
    Related proteins : CluSTrO14727
    Domain families : Pfam (Sanger)CARD (PF00619)    NB-ARC (PF00931)    WD40 (PF00400)   
    Domain families : Pfam (NCBI)pfam00619    pfam00931    pfam00400   
    Domain families : Smart (EMBL)WD40 (SM00320)  
    DMDM Disease mutations317
    Blocks (Seattle)O14727
    PDB (SRS)1C15    1CWW    1CY5    1Z6T    2P1H    2YGS    3J2T    3YGS   
    PDB (PDBSum)1C15    1CWW    1CY5    1Z6T    2P1H    2YGS    3J2T    3YGS   
    PDB (IMB)1C15    1CWW    1CY5    1Z6T    2P1H    2YGS    3J2T    3YGS   
    PDB (RSDB)1C15    1CWW    1CY5    1Z6T    2P1H    2YGS    3J2T    3YGS   
    Human Protein AtlasENSG00000120868
    Peptide AtlasO14727
    HPRD03755
    IPIIPI00023630   IPI00217460   IPI00217461   IPI00217462   IPI00217463   IPI00375875   IPI00953387   IPI01021762   
    Protein Interaction databases
    DIP (DOE-UCLA)O14727
    IntAct (EBI)O14727
    FunCoupENSG00000120868
    BioGRIDAPAF1
    IntegromeDBAPAF1
    STRING (EMBL)APAF1
    Ontologies - Pathways
    QuickGOO14727
    Ontology : AmiGOnucleotide binding  neural tube closure  protein binding  ATP binding  nucleus  cytosol  apoptotic DNA fragmentation  apoptotic process  activation of cysteine-type endopeptidase activity involved in apoptotic process  defense response  nervous system development  activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c  activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c  cysteine-type endopeptidase activator activity involved in apoptotic process  forebrain development  identical protein binding  regulation of apoptotic process  positive regulation of apoptotic process  apoptosome  apoptosome  ADP binding  neuron apoptotic process  extracellular vesicular exosome  response to G1 DNA damage checkpoint signaling  intrinsic apoptotic signaling pathway  positive regulation of apoptotic signaling pathway  
    Ontology : EGO-EBInucleotide binding  neural tube closure  protein binding  ATP binding  nucleus  cytosol  apoptotic DNA fragmentation  apoptotic process  activation of cysteine-type endopeptidase activity involved in apoptotic process  defense response  nervous system development  activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c  activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c  cysteine-type endopeptidase activator activity involved in apoptotic process  forebrain development  identical protein binding  regulation of apoptotic process  positive regulation of apoptotic process  apoptosome  apoptosome  ADP binding  neuron apoptotic process  extracellular vesicular exosome  response to G1 DNA damage checkpoint signaling  intrinsic apoptotic signaling pathway  positive regulation of apoptotic signaling pathway  
    Pathways : BIOCARTAHIV-I Nef: negative effector of Fas and TNF [Genes]    Trefoil Factors Initiate Mucosal Healing [Genes]    Caspase Cascade in Apoptosis [Genes]    Induction of apoptosis through DR3 and DR4/5 Death Receptors [Genes]    D4-GDI Signaling Pathway [Genes]    p53 Signaling Pathway [Genes]    Apoptotic Signaling in Response to DNA Damage [Genes]    Stress Induction of HSP Regulation [Genes]    Role of Mitochondria in Apoptotic Signaling [Genes]   
    Pathways : KEGGp53 signaling pathway    Apoptosis    Alzheimer's disease    Parkinson's disease    Amyotrophic lateral sclerosis (ALS)    Huntington's disease    Legionellosis    Tuberculosis    Hepatitis B    Small cell lung cancer   
    REACTOMEO14727 [protein]
    REACTOME PathwaysREACT_578 Apoptosis [pathway]
    Protein Interaction DatabaseAPAF1
    Wikipedia pathwaysAPAF1
    Gene fusion - rearrangments
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)APAF1
    SNP (GeneSNP Utah)APAF1
    SNP : HGBaseAPAF1
    Genetic variants : HAPMAPAPAF1
    1000_GenomesAPAF1 
    ICGC programENSG00000120868 
    CONAN: Copy Number AnalysisAPAF1 
    Somatic Mutations in Cancer : COSMICAPAF1 
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    DECIPHER (Syndromes)12:99039078-99129211
    Mutations and Diseases : HGMDAPAF1
    OMIM602233   
    MedgenAPAF1
    GENETestsAPAF1
    Disease Genetic AssociationAPAF1
    Huge Navigator APAF1 [HugePedia]  APAF1 [HugeCancerGEM]
    Genomic VariantsAPAF1  APAF1 [DGVbeta]
    Exome VariantAPAF1
    dbVarAPAF1
    ClinVarAPAF1
    snp3D : Map Gene to Disease317
    General knowledge
    Homologs : HomoloGeneAPAF1
    Homology/Alignments : Family Browser (UCSC)APAF1
    Phylogenetic Trees/Animal Genes : TreeFamAPAF1
    Chemical/Protein Interactions : CTD317
    Chemical/Pharm GKB GenePA24868
    Clinical trialAPAF1
    Cancer Resource (Charite)ENSG00000120868
    Other databases
    Probes
    Litterature
    PubMed140 Pubmed reference(s) in Entrez
    CoreMineAPAF1
    GoPubMedAPAF1
    iHOPAPAF1

    Bibliography

    Overexpression of Apaf-1 promotes apoptosis of untreated and paclitaxel- or etoposide-treated HL-60 cells.
    Perkins C, Kim CN, Fang G, Bhalla KN
    Cancer research. 1998 ; 58 (20) : 4561-4566.
    PMID 9788601
     
    Apaf1 and the apoptotic machinery.
    Cecconi F
    Cell death and differentiation. 1999 ; 6 (11) : 1087-1098.
    PMID 10578178
     
    Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition.
    Soengas MS, Alarcˆ„n RM, Yoshida H, Giaccia AJ, Hakem R, Mak TW, Lowe SW
    Science (New York, N.Y.). 1999 ; 284 (5411) : 156-159.
    PMID 10102818
     
    Expression and functional analysis of Apaf-1 isoforms. Extra Wd-40 repeat is required for cytochrome c binding and regulated activation of procaspase-9.
    Benedict MA, Hu Y, Inohara N, Nˆ†ˆ±ez G
    The Journal of biological chemistry. 2000 ; 275 (12) : 8461-8468.
    PMID 10722681
     
    Tumor suppressor genes.
    Macleod K
    Current opinion in genetics & development. 2000 ; 10 (1) : 81-93.
    PMID 10679386
     
    Efficacy of the chemotherapeutic action of HPMA copolymer-bound doxorubicin in a solid tumor model of ovarian carcinoma.
    Minko T, Kopeckovˆ° P, Kopecek J
    International journal of cancer. Journal international du cancer. 2000 ; 86 (1) : 108-117.
    PMID 10728603
     
    The role of Apaf-1, caspase-9, and bid proteins in etoposide- or paclitaxel-induced mitochondrial events during apoptosis.
    Perkins CL, Fang G, Kim CN, Bhalla KN
    Cancer research. 2000 ; 60 (6) : 1645-1653.
    PMID 10749135
     
    Evaluation of Apaf-1 and procaspases-2, -3, -7, -8, and -9 as potential prognostic markers in acute leukemia.
    Svingen PA, Karp JE, Krajewski S, Mesner PW Jr, Gore SD, Burke PJ, Reed JC, Lazebnik YA, Kaufmann SH
    Blood. 2000 ; 96 (12) : 3922-3931.
    PMID 11090079
     
    A comparison of the expression and properties of Apaf-1 and Apaf-1L.
    Walke DW, Morgan JI
    Brain research. 2000 ; 886 (1-2) : 73-81.
    PMID 11119689
     
    Frameshift mutations in Fas, Apaf-1, and Bcl-10 in gastro-intestinal cancer of the microsatellite mutator phenotype.
    Yamamoto H, Gil J, Schwartz S Jr, Perucho M
    Cell death and differentiation. 2000 ; 7 (2) : 238-239.
    PMID 10819600
     
    Proteasome inhibitor-induced apoptosis of B-chronic lymphocytic leukaemia cells involves cytochrome c release and caspase activation, accompanied by formation of an approximately 700 kDa Apaf-1 containing apoptosome complex.
    Almond JB, Snowden RT, Hunter A, Dinsdale D, Cain K, Cohen GM
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 ; 15 (9) : 1388-1397.
    PMID 11516099
     
    Apaf1 in developmental apoptosis and cancer: how many ways to die?
    Cecconi F, Gruss P
    Cellular and molecular life sciences : CMLS. 2001 ; 58 (11) : 1688-1697.
    PMID 11706994
     
    Apaf-1XL is an inactive isoform compared with Apaf-1L.
    Fu WN, Kelsey SM, Newland AC, Jia L
    Biochemical and biophysical research communications. 2001 ; 282 (1) : 268-272.
    PMID 11264002
     
    Frameshift mutations at mononucleotide repeats in RAD50 recombinational DNA repair gene in colorectal cancers with microsatellite instability.
    Ikenoue T, Togo G, Nagai K, Ijichi H, Kato J, Yamaji Y, Okamoto M, Kato N, Kawabe T, Tanaka A, Matsumura M, Shiratori Y, Omata M
    Japanese journal of cancer research : Gann. 2001 ; 92 (6) : 587-591.
    PMID 11429044
     
    Bax translocation is crucial for the sensitivity of leukaemic cells to etoposide-induced apoptosis.
    Jia L, Patwari Y, Srinivasula SM, Newland AC, Fernandes-Alnemri T, Alnemri ES, Kelsey SM
    Oncogene. 2001 ; 20 (35) : 4817-4826.
    PMID 11521193
     
    Apaf-1 protein deficiency confers resistance to cytochrome c-dependent apoptosis in human leukemic cells.
    Jia L, Srinivasula SM, Liu FT, Newland AC, Fernandes-Alnemri T, Alnemri ES, Kelsey SM
    Blood. 2001 ; 98 (2) : 414-421.
    PMID 11435311
     
    Preliminary evaluation of caspases-dependent apoptosis signaling pathways of free and HPMA copolymer-bound doxorubicin in human ovarian carcinoma cells.
    Minko T, Kopeckovˆ° P, Kopecek J
    Journal of controlled release : official journal of the Controlled Release Society. 2001 ; 71 (3) : 227-237.
    PMID 11295216
     
    Co-transduction of Apaf-1 and caspase-9 augments etoposide-induced apoptosis in U-373MG glioma cells.
    Shinoura N, Sakurai S, Asai A, Kirino T, Hamada H
    Japanese journal of cancer research : Gann. 2001 ; 92 (4) : 467-474.
    PMID 11346470
     
    Over-expression of APAF-1 and caspase-9 augments radiation-induced apoptosis in U-373MG glioma cells.
    Shinoura N, Sakurai S, Asai A, Kirino T, Hamada H
    International journal of cancer. Journal international du cancer. 2001 ; 93 (2) : 252-261.
    PMID 11410874
     
    Inactivation of the apoptosis effector Apaf-1 in malignant melanoma.
    Soengas MS, Capodieci P, Polsky D, Mora J, Esteller M, Opitz-Araya X, McCombie R, Herman JG, Gerald WL, Lazebnik YA, Cordˆ„n-Cardˆ„ C, Lowe SW
    Nature. 2001 ; 409 (6817) : 207-211.
    PMID 11196646
     
    Defective cytochrome c-dependent caspase activation in ovarian cancer cell lines due to diminished or absent apoptotic protease activating factor-1 activity.
    Wolf BB, Schuler M, Li W, Eggers-Sedlet B, Lee W, Tailor P, Fitzgerald P, Mills GB, Green DR
    The Journal of biological chemistry. 2001 ; 276 (36) : 34244-34251.
    PMID 11429402
     
    Apoptosomes: engines for caspase activation.
    Adams JM, Cory S
    Current opinion in cell biology. 2002 ; 14 (6) : 715-720.
    PMID 12473344
     
    Transcriptional and physiological responses of HepG2 cells exposed to diethyl maleate: time course analysis.
    Casey W, Anderson S, Fox T, Dold K, Colton H, Morgan K
    Physiological genomics. 2002 ; 8 (2) : 115-122.
    PMID 11875189
     
    Apoptosis: molecular regulation of cell death and hematologic malignancies.
    Chiarugi V, Cinelli M, Magnelli L, Dello SP
    Molecular biotechnology. 2002 ; 20 (3) : 305-314.
    PMID 11936259
     
    Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours.
    Esteller M, Herman JG
    The Journal of pathology. 2002 ; 196 (1) : 1-7.
    PMID 11748635
     
    Apaf-1 is a mediator of E2F-1-induced apoptosis.
    Furukawa Y, Nishimura N, Furukawa Y, Satoh M, Endo H, Iwase S, Yamada H, Matsuda M, Kano Y, Nakamura M
    The Journal of biological chemistry. 2002 ; 277 (42) : 39760-39768.
    PMID 12149244
     
    Dysfunctional apoptosome activation in ovarian cancer: implications for chemoresistance.
    Liu JR, Opipari AW, Tan L, Jiang Y, Zhang Y, Tang H, Nuˆ±ez G
    Cancer research. 2002 ; 62 (3) : 924-931.
    PMID 11830553
     
    Enhancing the anticancer efficacy of camptothecin using biotinylated poly(ethylene glycol) conjugates in sensitive and multidrug-resistant human ovarian carcinoma cells.
    Minko T, Paranjpe PV, Qiu B, Lalloo A, Won R, Stein S, Sinko PJ
    Cancer chemotherapy and pharmacology. 2002 ; 50 (2) : 143-150.
    PMID 12172980
     
    Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants.
    Narayanan BA, Narayanan NK, Stoner GD, Bullock BP
    Life sciences. 2002 ; 70 (15) : 1821-1839.
    PMID 12002526
     
    Regulation of apoptosis by p53 in UV-irradiated human epidermis, psoriatic plaques and senescent keratinocytes.
    Qin JZ, Chaturvedi V, Denning MF, Bacon P, Panella J, Choubey D, Nickoloff BJ
    Oncogene. 2002 ; 21 (19) : 2991-3002.
    PMID 12082529
     
    Co-transduction of Apaf-1 and caspase-9 highly enhances p53-mediated apoptosis in gliomas.
    Shinoura N, Sakurai S, Shibasaki F, Asai A, Kirino T, Hamada H
    British journal of cancer. 2002 ; 86 (4) : 587-595.
    PMID 11870542
     
    Caspase-9 and Apaf-1 are expressed and functionally active in human neuroblastoma tumor cell lines with 1p36 LOH and amplified MYCN.
    Teitz T, Wei T, Liu D, Valentine V, Valentine M, Grenet J, Lahti JM, Kidd VJ
    Oncogene. 2002 ; 21 (12) : 1848-1858.
    PMID 11896617
     
    Methylation profiling of twenty promoter-CpG islands of genes which may contribute to hepatocellular carcinogenesis.
    Yu J, Ni M, Xu J, Zhang H, Gao B, Gu J, Chen J, Zhang L, Wu M, Zhen S, Zhu J
    BMC cancer. 2002 ; 2 : page 29.
    PMID 12433278
     
    Hairy-cell leukaemia as a model for drug development.
    Carson DA, Leoni LM
    Best practice & research. Clinical haematology. 2003 ; 16 (1) : 83-89.
    PMID 12670467
     
    Molecular targeting of drug delivery systems to ovarian cancer by BH3 and LHRH peptides.
    Dharap SS, Qiu B, Williams GC, Sinko P, Stein S, Minko T
    Journal of controlled release : official journal of the Controlled Release Society. 2003 ; 91 (1-2) : 61-73.
    PMID 12932638
     
    Physiological and pathological roles of Apaf1 and the apoptosome.
    Ferraro E, Corvaro M, Cecconi F
    Journal of cellular and molecular medicine. 2003 ; 7 (1) : 21-34.
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    Contributor(s)

    Written09-2004Marco Corvaro, Francesco Cecconi
    "Dulbecco Telethon Institute,Department of Biology, University of Rome ""Tor Vergata"", Via della Ricerca Scientifica, 00133 Rome, Italy"

    Citation

    This paper should be referenced as such :
    Corvaro, M ; Cecconi, F
    APAF1 (apoptotic protease activating factor 1)
    Atlas Genet Cytogenet Oncol Haematol. 2004;8(4):289-293.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Genes/APAF1ID422.html

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