- 関
- apoptotic protease-activating factor 1
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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2016/11/03 21:02:42」(JST)
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APAF1 |
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Available structures |
PDB |
Ortholog search: PDBe RCSB |
List of PDB id codes |
1C15, 1CWW, 1CY5, 1Z6T, 2P1H, 2YGS, 3J2T, 3YGS, 4RHW, 3JBT
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Identifiers |
Aliases |
APAF1, APAF-1, CED4, apoptotic peptidase activating factor 1 |
External IDs |
MGI: 1306796 HomoloGene: 7626 GeneCards: APAF1 |
Gene ontology |
Molecular function |
• heat shock protein binding
• ADP binding
• protein binding
• identical protein binding
• ATP binding
• nucleotide binding
• cysteine-type endopeptidase activator activity involved in apoptotic process
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Cellular component |
• cytoplasm
• cytosol
• extracellular exosome
• nucleus
• apoptosome
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Biological process |
• cellular response to transforming growth factor beta stimulus
• neuron apoptotic process
• regulation of apoptotic process
• cell differentiation
• response to hypoxia
• response to nutrient
• response to G1 DNA damage checkpoint signaling
• aging
• positive regulation of apoptotic signaling pathway
• glial cell apoptotic process
• nervous system development
• multicellular organism development
• cardiac muscle cell apoptotic process
• intrinsic apoptotic signaling pathway
• intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
• neural tube closure
• brain development
• positive regulation of apoptotic process
• apoptotic signaling pathway
• forebrain development
• regulation of apoptotic DNA fragmentation
• protein homooligomerization
• activation of cysteine-type endopeptidase activity involved in apoptotic process
• activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c
• apoptotic process
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Sources:Amigo / QuickGO |
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RNA expression pattern |
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More reference expression data |
Orthologs |
Species |
Human |
Mouse |
Entrez |
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Ensembl |
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UniProt |
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RefSeq (mRNA) |
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NM_001160
NM_013229
NM_181861
NM_181868
NM_181869
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NM_001042558
NM_001282947
NM_009684
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RefSeq (protein) |
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NP_001151.1
NP_037361.1
NP_863651.1
NP_863658.1
NP_863659.1
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NP_001036023.1
NP_033814.2
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Location (UCSC) |
Chr 12: 98.65 – 98.74 Mb |
Chr 10: 90.99 – 91.08 Mb |
PubMed search |
[1] |
[2] |
Wikidata |
View/Edit Human |
View/Edit Mouse |
Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.[3][4][5]
Contents
- 1 Function
- 2 Structure
- 3 Interactions
- 4 References
- 5 Further reading
Function
This gene encodes a cytoplasmic protein that forms one of the central hubs in the apoptosis regulatory network. This protein contains (from the N terminal) a caspase recruitment domain (CARD), an ATPase domain (NB-ARC), few short helical domains and then several copies of the WD40 repeat domain. Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves Procaspase 9 protein, releasing its mature, activated form. The precise mechanism for this reaction is still debated though work published by Guy Salvesen suggests that the apoptosome may induce caspase 9 dimerization and subsequent autocatalysis.[6] Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.
Alternative splicing results in several transcript variants encoding different isoforms.[3]
Structure
APAF1 contains a Greek key motif composed of six helices, a Rossman fold nucleotide binding domains, a short helical motif and a winged-helix domain.[7] It contains a CARD domain with a
Interactions
APAF1 has been shown to interact with:
- APIP,[8]
- BCL2-like 1[9][10]
- Caspase-9,[11][8][12][9][10]
- HSPA4,[13] and
- NLRP1.[11]
References
- ^ "Human PubMed Reference:".
- ^ "Mouse PubMed Reference:".
- ^ a b "Entrez Gene: APAF1 apoptotic peptidase activating factor 1".
- ^ Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (Aug 1997). "Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3". Cell. 90 (3): 405–13. doi:10.1016/S0092-8674(00)80501-2. PMID 9267021.
- ^ Kim H, Jung YK, Kwon YK, Park SH (1999). "Assignment of apoptotic protease activating factor-1 gene (APAF1) to human chromosome band 12q23 by fluorescence in situ hybridization". Cytogenetics and Cell Genetics. 87 (3-4): 252–3. doi:10.1159/000015436. PMID 10702682.
- ^ Pop C, Timmer J, Sperandio S, Salvesen GS (Apr 2006). "The apoptosome activates caspase-9 by dimerization". Molecular Cell. 22 (2): 269–75. doi:10.1016/j.molcel.2006.03.009. PMID 16630894.
- ^ Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y (Apr 2005). "Structure of the apoptotic protease-activating factor 1 bound to ADP". Nature. 434 (7035): 926–33. doi:10.1038/nature03465. PMID 15829969.
- ^ a b Cho DH, Hong YM, Lee HJ, Woo HN, Pyo JO, Mak TW, Jung YK (Sep 2004). "Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein". The Journal of Biological Chemistry. 279 (38): 39942–50. doi:10.1074/jbc.M405747200. PMID 15262985.
- ^ a b Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation". Proceedings of the National Academy of Sciences of the United States of America. 95 (8): 4386–91. doi:10.1073/pnas.95.8.4386. PMC 22498. PMID 9539746.
- ^ a b Pan G, O'Rourke K, Dixit VM (Mar 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". The Journal of Biological Chemistry. 273 (10): 5841–5. doi:10.1074/jbc.273.10.5841. PMID 9488720.
- ^ a b Chu ZL, Pio F, Xie Z, Welsh K, Krajewska M, Krajewski S, Godzik A, Reed JC (Mar 2001). "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". The Journal of Biological Chemistry. 276 (12): 9239–45. doi:10.1074/jbc.M006309200. PMID 11113115.
- ^ Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (Nov 1997). "Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade". Cell. 91 (4): 479–89. doi:10.1016/s0092-8674(00)80434-1. PMID 9390557.
- ^ Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES (Aug 2000). "Negative regulation of the Apaf-1 apoptosome by Hsp70". Nature Cell Biology. 2 (8): 476–83. doi:10.1038/35019510. PMID 10934467.
Further reading
- Smith TF, Gaitatzes C, Saxena K, Neer EJ (May 1999). "The WD repeat: a common architecture for diverse functions". Trends in Biochemical Sciences. 24 (5): 181–5. doi:10.1016/S0968-0004(99)01384-5. PMID 10322433.
- van Oirschot JT (Aug 1999). "Diva vaccines that reduce virus transmission". Journal of Biotechnology. 73 (2-3): 195–205. doi:10.1016/S0168-1656(99)00121-2. PMID 10486928.
- Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (Jun 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
- Campioni M, Santini D, Tonini G, Murace R, Dragonetti E, Spugnini EP, Baldi A (Nov 2005). "Role of Apaf-1, a key regulator of apoptosis, in melanoma progression and chemoresistance". Experimental Dermatology. 14 (11): 811–8. doi:10.1111/j.1600-0625.2005.00360.x. PMID 16232302.
- Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (Aug 1997). "Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3". Cell. 90 (3): 405–13. doi:10.1016/S0092-8674(00)80501-2. PMID 9267021.
- Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (Nov 1997). "Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade". Cell. 91 (4): 479–89. doi:10.1016/S0092-8674(00)80434-1. PMID 9390557.
- Ishikawa K, Nagase T, Nakajima D, Seki N, Ohira M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Oct 1997). "Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 4 (5): 307–13. doi:10.1093/dnares/4.5.307. PMID 9455477.
- Pan G, O'Rourke K, Dixit VM (Mar 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". The Journal of Biological Chemistry. 273 (10): 5841–5. doi:10.1074/jbc.273.10.5841. PMID 9488720.
- Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation". Proceedings of the National Academy of Sciences of the United States of America. 95 (8): 4386–91. doi:10.1073/pnas.95.8.4386. PMC 22498. PMID 9539746.
- Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Alnemri ES (Jun 1998). "Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization". Molecular Cell. 1 (7): 949–57. doi:10.1016/S1097-2765(00)80095-7. PMID 9651578.
- Cecconi F, Alvarez-Bolado G, Meyer BI, Roth KA, Gruss P (Sep 1998). "Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development". Cell. 94 (6): 727–37. doi:10.1016/S0092-8674(00)81732-8. PMID 9753320.
- Inohara N, Gourley TS, Carrio R, Muñiz M, Merino J, Garcia I, Koseki T, Hu Y, Chen S, Núñez G (Dec 1998). "Diva, a Bcl-2 homologue that binds directly to Apaf-1 and induces BH3-independent cell death". The Journal of Biological Chemistry. 273 (49): 32479–86. doi:10.1074/jbc.273.49.32479. PMID 9829980.
- Hu Y, Ding L, Spencer DM, Núñez G (Dec 1998). "WD-40 repeat region regulates Apaf-1 self-association and procaspase-9 activation". The Journal of Biological Chemistry. 273 (50): 33489–94. doi:10.1074/jbc.273.50.33489. PMID 9837928.
- Song Q, Kuang Y, Dixit VM, Vincenz C (Jan 1999). "Boo, a novel negative regulator of cell death, interacts with Apaf-1". The EMBO Journal. 18 (1): 167–78. doi:10.1093/emboj/18.1.167. PMC 1171112. PMID 9878060.
- Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ (Jan 1999). "Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner". The Journal of Cell Biology. 144 (2): 281–92. doi:10.1083/jcb.144.2.281. PMC 2132895. PMID 9922454.
- Zou H, Li Y, Liu X, Wang X (Apr 1999). "An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9". The Journal of Biological Chemistry. 274 (17): 11549–56. doi:10.1074/jbc.274.17.11549. PMID 10206961.
- Saleh A, Srinivasula SM, Acharya S, Fishel R, Alnemri ES (Jun 1999). "Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9 activation". The Journal of Biological Chemistry. 274 (25): 17941–5. doi:10.1074/jbc.274.25.17941. PMID 10364241.
- Qin H, Srinivasula SM, Wu G, Fernandes-Alnemri T, Alnemri ES, Shi Y (Jun 1999). "Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1". Nature. 399 (6736): 549–57. doi:10.1038/21124. PMID 10376594.
- Drosopoulos NE, Walsh FS, Doherty P (Jun 1999). "A soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates neurite outgrowth via a Grb2/MEK1-dependent signaling cascade". Molecular and Cellular Neurosciences. 13 (6): 441–9. doi:10.1006/mcne.1999.0758. PMID 10383829.
PDB gallery
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1c15: SOLUTION STRUCTURE OF APAF-1 CARD
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1cww: SOLUTION STRUCTURE OF THE CASPASE RECRUITMENT DOMAIN (CARD) FROM APAF-1
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1cy5: CRYSTAL STRUCTURE OF THE APAF-1 CARD
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1z6t: Structure of the apoptotic protease-activating factor 1 bound to ADP
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2p1h: Rapid Folding and Unfolding of Apaf-1 CARD
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2ygs: CARD DOMAIN FROM APAF-1
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3ygs: APAF-1 CARD IN COMPLEX WITH PRODOMAIN OF PROCASPASE-9
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UpToDate Contents
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English Journal
- MicroRNA-125b-2 confers human glioblastoma stem cells resistance to temozolomide through the mitochondrial pathway of apoptosis.
- Shi L, Zhang S, Feng K, Wu F, Wan Y, Wang Z, Zhang J, Wang Y, Yan W, Fu Z, You Y.SourceDepartment of Neurosurgery, The First People's Hospital of Kunshan affiliated with Jiangsu University, Suzhou 15300, P.R. China. shileigff@126.com
- International journal of oncology.Int J Oncol.2012 Jan;40(1):119-29. doi: 10.3892/ijo.2011.1179. Epub 2011 Aug 29.
- MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs. miR-125b, one of the neuronal miRNAs, was recently found to be necessary for stem cell fission and for making stem ce
- PMID 21879257
- Acacetin induces apoptosis in human T cell leukemia Jurkat cells via activation of a caspase cascade.
- Watanabe K, Kanno S, Tomizawa A, Yomogida S, Ishikawa M.SourceDepartment of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aobaku, Sendai 981-8553, Japan.
- Oncology reports.Oncol Rep.2012 Jan;27(1):204-9. doi: 10.3892/or.2011.1498. Epub 2011 Oct 12.
- Flavonoids are naturally occurring antioxidants, with several flavonoids shown to have chemopreventive effects on cancer. We investigated the effects of the flavonoid acacetin on human T cell leukemia Jurkat cells. Acacetin inhibited the proliferation of Jurkat ce
- PMID 21993665
Japanese Journal
- Sequence Fourier Analysis of a Specific Protein–DNA (RNA) Interaction; an Intermolecular Frequency Symmetry
- Numao Naganori,Kamimoto Yoshihito
- CHEMICAL & PHARMACEUTICAL BULLETIN 57(11), 1305-1307, 2009
- … Here, we first report that a specific protein–DNA (RNA) interaction between p53 protein and divergent I kappa B kinase interacting protein (IKIP)-Apaf1 DNA promoter region, and between poliovirus 3CD protein and the 5′ terminal region of the RNA sequence can be successfully elucidated with a sequence Fourier analysis, alike various specific protein–protein interactions described previously. …
- NAID 130000124830
- Rapid and significant induction of TRAIL-mediated type II cells in apoptosis of primary salivary epithelial cells in primary Sjögren's syndrome.
- Nakamura Hideki,Kawakami Atsushi,Iwamoto Naoki,Ida Hiroaki,Koji Takehiko,Eguchi Katsumi
- Apoptosis : an international journal on programmed cell death 13(11), 1322-1330, 2008-11
- … Activation of caspases, cytochrome C, and apoptotic protease activating factor-1 (Apaf-1) was determined by western blotting or immunofluorescence observed by confocal microscopy. … TRAIL-induced caspase 9 cleavage accompanied by activation of cytochrome C and Apaf-1 were not mediated by anti-Fas antibody. …
- NAID 120001700149
Related Links
- 免疫炎症制御研究分野ホームへ Apaf-1 様蛋白:新しい炎症と細胞死シグナルの接点 Apaf-1 like proteins at a crossroads of apoptosis and inflammation 細胞工学第 24 巻、 No.9 、 929 - 933 頁 2005 年 須田貴司 Takashi ...
- 新しいアポトーシス・炎症関連蛋白群、 NLR ファミリーの研究 最近 apoptotic protease-activating factor (Apaf)-1 と類似の構造をもつ 20 種類を越す蛋白質が発見され、それらが炎症とアポトーシスの誘導や制御に働く分子であることが明らかに ...
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★リンクテーブル★
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アポトーシスプロテアーゼ活性化因子1
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[★]
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- apoptotic protease-activating factor 1、Apaf-1