Apaf-1

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Apoptotic protease-activating factor 1
Apoptotic protease-activating factor 1
Apaf-1

Existing structure data : PDB  1C15 , PDB  1CWW , PDB  1CY5

Properties of human protein
Mass / length primary structure 1,248 amino acids , 141,840 Da
Identifier
External IDs
Orthologue (human)
Entrez 317
Ensemble ENSG00000120868
UniProt O14727
Refseq (mRNA) NM_001160.2
Refseq (protein) NP_001151.1
PubMed search 317

Apaf-1 is a protein that plays a role in initiating programmed cell death (apoptosis).

properties

In the intrinsic or mitochondrial path of apoptosis, stress signals lead to inactivation of the protein Bcl-2 . The inactivation of this anti-apoptotic factor leads to apoptosis.

Active Bcl-2 prevents the deposition of a dimer of the proteins Bak and Bax on the mitochondrial outer membrane . By inactivating Bcl-2, the Bak-Bax dimer attaches to the mitochondrial outer membrane and a pore is formed in the outer mitochondrial membrane. Through this pore formation, cytochrome c moves from the mitochondrion into the cytosol. This localization of cytochrome c in the non-original location is a signal of apoptosis, because cytochrome c binds to Apaf-1 in the cytosol. The binding of cytochrome c to Apaf-1 creates the apoptosome ("The wheel of death"). The apoptosome activates the initiator caspase pro-caspase 9, which then autocatalytically cleaves itself and then activates further caspases by cleavage. The breakdown of proteins is initiated by the caspase cascade.

Apaf-1 binds to APIP , BCL2-like 1 caspase-9 , HSPA4 , and NLRP1 .

Apaf-1 is produced in all cell types. Most of it is produced in the adult spleen and peripheral leukocytes , as well as in the fetal brain , kidney and lungs . The isoform 1 is in the heart formed. Isoform 6 activates pro-caspase 9 less.

Structurally containing Apaf-1 is a CARD domain with a greek key six-helix, a Rossmann fold for binding of nucleotides , followed by a short helical motif and a winged-helix - protein domain . Apaf-1 is the homologue of ced-4 from Caenorhabditis elegans .

Web links

Individual evidence

  1. ↑ a b Cho DH, Hong YM, Lee HJ, Woo HN, Pyo JO, Mak TW, Jung YK: Induced inhibition of ischemic / hypoxic injury by APIP, a novel Apaf-1-interacting protein . In: The Journal of Biological Chemistry . 279, No. 38, Sep 2004, pp. 39942-50. doi : 10.1074 / jbc.M405747200 . PMID 15262985 .
  2. ↑ a b Hu Y, Benedict MA, Wu D, Inohara N, Núñez G: Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation . In: Proceedings of the National Academy of Sciences . 95, No. 8, Apr 1998, pp. 4386-91. doi : 10.1073 / pnas.95.8.4386 . PMID 9539746 . PMC 22498 (free full text).
  3. ^ A b Pan G, O'Rourke K, Dixit VM: Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex . In: The Journal of Biological Chemistry . 273, No. 10, Mar 1998, pp. 5841-5. doi : 10.1074 / jbc.273.10.5841 . PMID 9488720 .
  4. ↑ a b Chu ZL, Pio F, Xie Z, Welsh K, Krajewska M, Krajewski S, Godzik A, Reed JC: A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis . In: The Journal of Biological Chemistry . 276, No. 12, Mar 2001, pp. 9239-45. doi : 10.1074 / jbc.M006309200 . PMID 11113115 .
  5. ↑ Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X: Cytochrome c and dATP-dependent formation of Apaf-1 / caspase-9 complex initiates an apoptotic protease cascade . In: Cell . 91, No. 4, Nov 1997, pp. 479-89. doi : 10.1016 / s0092-8674 (00) 80434-1 . PMID 9390557 .
  6. ↑ Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES: Negative regulation of the Apaf-1 apoptosome by Hsp70 . In: Nature Cell Biology . 2, No. 8, Aug 2000, pp. 476-83. doi : 10.1038 / 35019510 . PMID 10934467 .
  7. ↑ Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y: Structure of the apoptotic protease-activating factor 1 bound to ADP . In: Nature . 434, No. 7035, Apr 2005, pp. 926-33. doi : 10.1038 / nature03465 . PMID 15829969 .
  8. ↑ H. Zou, WJ Henzel, X. Liu, A. Lutschg, X. Wang: Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. In: Cell. Volume 90, Number 3, August 1997, pp. 405-413, PMID 9267021 .