ア・トーシスプロテアーゼ活性化因子1

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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Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.^[3]^[4]^[5]

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.

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

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★リンクテーブル★

リンク元	「apoptotic protease-activating factor 1」「アポトーシスプロテアーゼ活性化因子1」

「apoptotic protease-activating factor 1」

APAF1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1C15, 1CWW, 1CY5, 1Z6T, 2P1H, 2YGS, 3J2T, 3YGS, 4RHW, 3JBT
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;
Cellular component	• cytoplasm; • cytosol; • extracellular exosome; • nucleus; • apoptosome;
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;
	Sources:Amigo / QuickGO
RNA expression pattern
	; ; ; ;
	More reference expression data
Orthologs
	317
	11783
	ENSG00000120868
	ENSMUSG00000019979
	O14727
	O88879
	NM_001160; NM_013229; NM_181861; NM_181868; NM_181869
	NM_001042558; NM_001282947; NM_009684
	NP_001151.1; NP_037361.1; NP_863651.1; NP_863658.1; NP_863659.1
	NP_001036023.1; NP_033814.2
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

アポトーシスプロテアーゼ活性化因子1

関: Apaf-1

「アポトーシスプロテアーゼ活性化因子1」

　　[★]

英: apoptotic protease-activating factor 1、Apaf-1

[1] "Human PubMed Reference:".

[2] "Mouse PubMed Reference:".

[entrez-3] "Entrez Gene: APAF1 apoptotic peptidase activating factor 1".

[pmid9267021-4] 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.

[pmid10702682-5] 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.

[pmid16630894-6] 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.

[pmid15829969-7] 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.

[pmid15262985-8] 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.

[pmid9539746-9] 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.

[pmid9488720-10] 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.

[pmid11113115-11] 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.

[pmid9390557-12] 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.

[pmid10934467-13] 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.

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Apaf-1