| 释义 |
- Function
- Structure
- Interactions
- References
- External links
- Further reading
{{Infobox_gene}}Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.[1][1][2] 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.[3] Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results in several transcript variants encoding different isoforms.[4] Structure APAF1 contains a CARD domain with a Greek key motif composed of six helices, a Rossman fold nucleotide binding domains, a short helical motif and a winged-helix domain.[5] Interactions APAF1 has been shown to interact with: - APIP,[7]
- BCL2-like 1[8][9]
- Caspase-9,[10][6][7][8][9]
- HSPA4,[10] and
- NLRP1.[11]
References 1. ^{{cite journal | vauthors = Zou H, Henzel WJ, Liu X, Lutschg A, Wang X | title = Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3 | journal = Cell | volume = 90 | issue = 3 | pages = 405–13 | date = Aug 1997 | pmid = 9267021 | doi = 10.1016/S0092-8674(00)80501-2 }}
2. ^{{cite journal | vauthors = Kim H, Jung YK, Kwon YK, Park SH | title = Assignment of apoptotic protease activating factor-1 gene (APAF1) to human chromosome band 12q23 by fluorescence in situ hybridization | journal = Cytogenetics and Cell Genetics | volume = 87 | issue = 3–4 | pages = 252–3 | year = 1999 | pmid = 10702682 | doi = 10.1159/000015436 }}
3. ^{{cite journal | vauthors = Pop C, Timmer J, Sperandio S, Salvesen GS | title = The apoptosome activates caspase-9 by dimerization | journal = Molecular Cell | volume = 22 | issue = 2 | pages = 269–75 | date = Apr 2006 | pmid = 16630894 | doi = 10.1016/j.molcel.2006.03.009 }}
4. ^1 {{Cite web| title = Entrez Gene: APAF1 apoptotic peptidase activating factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=317| accessdate = }}
5. ^{{cite journal | vauthors = Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y | title = Structure of the apoptotic protease-activating factor 1 bound to ADP | journal = Nature | volume = 434 | issue = 7035 | pages = 926–33 | date = Apr 2005 | pmid = 15829969 | doi = 10.1038/nature03465 }}
6. ^1 {{cite journal | vauthors = Cho DH, Hong YM, Lee HJ, Woo HN, Pyo JO, Mak TW, Jung YK | title = Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein | journal = The Journal of Biological Chemistry | volume = 279 | issue = 38 | pages = 39942–50 | date = Sep 2004 | pmid = 15262985 | doi = 10.1074/jbc.M405747200 }}
7. ^{{cite journal | vauthors = Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X | title = Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade | journal = Cell | volume = 91 | issue = 4 | pages = 479–89 | date = Nov 1997 | pmid = 9390557 | doi = 10.1016/s0092-8674(00)80434-1}}
8. ^1 {{cite journal | vauthors = Hu Y, Benedict MA, Wu D, Inohara N, Núñez G | title = Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 8 | pages = 4386–91 | date = Apr 1998 | pmid = 9539746 | pmc = 22498 | doi = 10.1073/pnas.95.8.4386}}
9. ^1 {{cite journal | vauthors = Pan G, O'Rourke K, Dixit VM | title = Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex | journal = The Journal of Biological Chemistry | volume = 273 | issue = 10 | pages = 5841–5 | date = Mar 1998 | pmid = 9488720 | doi = 10.1074/jbc.273.10.5841}}
10. ^{{cite journal | vauthors = Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES | title = Negative regulation of the Apaf-1 apoptosome by Hsp70 | journal = Nature Cell Biology | volume = 2 | issue = 8 | pages = 476–83 | date = Aug 2000 | pmid = 10934467 | doi = 10.1038/35019510 }}
11. ^1 {{cite journal | vauthors = Chu ZL, Pio F, Xie Z, Welsh K, Krajewska M, Krajewski S, Godzik A, Reed JC | title = A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis | journal = The Journal of Biological Chemistry | volume = 276 | issue = 12 | pages = 9239–45 | date = Mar 2001 | pmid = 11113115 | doi = 10.1074/jbc.M006309200 }}
{{-}}External links Further reading {{Refbegin|33em}}- {{cite journal | vauthors = Smith TF, Gaitatzes C, Saxena K, Neer EJ | title = The WD repeat: a common architecture for diverse functions | journal = Trends in Biochemical Sciences | volume = 24 | issue = 5 | pages = 181–5 | date = May 1999 | pmid = 10322433 | doi = 10.1016/S0968-0004(99)01384-5 }}
- {{cite journal | vauthors = van Oirschot JT | title = Diva vaccines that reduce virus transmission | journal = Journal of Biotechnology | volume = 73 | issue = 2–3 | pages = 195–205 | date = Aug 1999 | pmid = 10486928 | doi = 10.1016/S0168-1656(99)00121-2 }}
- {{cite journal | vauthors = Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T | title = Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones | journal = DNA Research | volume = 9 | issue = 3 | pages = 99–106 | date = Jun 2002 | pmid = 12168954 | doi = 10.1093/dnares/9.3.99 }}
- {{cite journal | vauthors = Campioni M, Santini D, Tonini G, Murace R, Dragonetti E, Spugnini EP, Baldi A | title = Role of Apaf-1, a key regulator of apoptosis, in melanoma progression and chemoresistance | journal = Experimental Dermatology | volume = 14 | issue = 11 | pages = 811–8 | date = Nov 2005 | pmid = 16232302 | doi = 10.1111/j.1600-0625.2005.00360.x }}
- {{cite journal | vauthors = Zou H, Henzel WJ, Liu X, Lutschg A, Wang X | title = Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3 | journal = Cell | volume = 90 | issue = 3 | pages = 405–13 | date = Aug 1997 | pmid = 9267021 | doi = 10.1016/S0092-8674(00)80501-2 }}
- {{cite journal | vauthors = Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X | title = Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade | journal = Cell | volume = 91 | issue = 4 | pages = 479–89 | date = Nov 1997 | pmid = 9390557 | doi = 10.1016/S0092-8674(00)80434-1 }}
- {{cite journal | vauthors = Ishikawa K, Nagase T, Nakajima D, Seki N, Ohira M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro | journal = DNA Research | volume = 4 | issue = 5 | pages = 307–13 | date = Oct 1997 | pmid = 9455477 | doi = 10.1093/dnares/4.5.307 }}
- {{cite journal | vauthors = Pan G, O'Rourke K, Dixit VM | title = Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex | journal = The Journal of Biological Chemistry | volume = 273 | issue = 10 | pages = 5841–5 | date = Mar 1998 | pmid = 9488720 | doi = 10.1074/jbc.273.10.5841 }}
- {{cite journal | vauthors = Hu Y, Benedict MA, Wu D, Inohara N, Núñez G | title = Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 8 | pages = 4386–91 | date = Apr 1998 | pmid = 9539746 | pmc = 22498 | doi = 10.1073/pnas.95.8.4386 }}
- {{cite journal | vauthors = Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Alnemri ES | title = Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization | journal = Molecular Cell | volume = 1 | issue = 7 | pages = 949–57 | date = Jun 1998 | pmid = 9651578 | doi = 10.1016/S1097-2765(00)80095-7 }}
- {{cite journal | vauthors = Cecconi F, Alvarez-Bolado G, Meyer BI, Roth KA, Gruss P | title = Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development | journal = Cell | volume = 94 | issue = 6 | pages = 727–37 | date = Sep 1998 | pmid = 9753320 | doi = 10.1016/S0092-8674(00)81732-8 }}
- {{cite journal | vauthors = Inohara N, Gourley TS, Carrio R, Muñiz M, Merino J, Garcia I, Koseki T, Hu Y, Chen S, Núñez G | title = Diva, a Bcl-2 homologue that binds directly to Apaf-1 and induces BH3-independent cell death | journal = The Journal of Biological Chemistry | volume = 273 | issue = 49 | pages = 32479–86 | date = Dec 1998 | pmid = 9829980 | doi = 10.1074/jbc.273.49.32479 }}
- {{cite journal | vauthors = Hu Y, Ding L, Spencer DM, Núñez G | title = WD-40 repeat region regulates Apaf-1 self-association and procaspase-9 activation | journal = The Journal of Biological Chemistry | volume = 273 | issue = 50 | pages = 33489–94 | date = Dec 1998 | pmid = 9837928 | doi = 10.1074/jbc.273.50.33489 }}
- {{cite journal | vauthors = Song Q, Kuang Y, Dixit VM, Vincenz C | title = Boo, a novel negative regulator of cell death, interacts with Apaf-1 | journal = The EMBO Journal | volume = 18 | issue = 1 | pages = 167–78 | date = Jan 1999 | pmid = 9878060 | pmc = 1171112 | doi = 10.1093/emboj/18.1.167 }}
- {{cite journal | vauthors = Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ | title = Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner | journal = The Journal of Cell Biology | volume = 144 | issue = 2 | pages = 281–92 | date = Jan 1999 | pmid = 9922454 | pmc = 2132895 | doi = 10.1083/jcb.144.2.281 }}
- {{cite journal | vauthors = Zou H, Li Y, Liu X, Wang X | title = An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 17 | pages = 11549–56 | date = Apr 1999 | pmid = 10206961 | doi = 10.1074/jbc.274.17.11549 }}
- {{cite journal | vauthors = Saleh A, Srinivasula SM, Acharya S, Fishel R, Alnemri ES | title = Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9 activation | journal = The Journal of Biological Chemistry | volume = 274 | issue = 25 | pages = 17941–5 | date = Jun 1999 | pmid = 10364241 | doi = 10.1074/jbc.274.25.17941 }}
- {{cite journal | vauthors = Qin H, Srinivasula SM, Wu G, Fernandes-Alnemri T, Alnemri ES, Shi Y | title = Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1 | journal = Nature | volume = 399 | issue = 6736 | pages = 549–57 | date = Jun 1999 | pmid = 10376594 | doi = 10.1038/21124 }}
- {{cite journal | vauthors = Drosopoulos NE, Walsh FS, Doherty P | title = A soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates neurite outgrowth via a Grb2/MEK1-dependent signaling cascade | journal = Molecular and Cellular Neurosciences | volume = 13 | issue = 6 | pages = 441–9 | date = Jun 1999 | pmid = 10383829 | doi = 10.1006/mcne.1999.0758 }}
{{Refend}}{{PDB Gallery|geneid=317}}{{DEFAULTSORT:Apaf1}} 2 : Programmed cell death|Apoptosis |