Alternative titles; symbols
HGNC Approved Gene Symbol: AVEN
Cytogenetic location: 15q14 Genomic coordinates (GRCh38): 15:33,851,781-34,075,325 (from NCBI)
BCLXL (600039), an antiapoptotic BCL2 family member, is postulated to function at multiple stages in the cell death pathway. The possibility that BCLXL inhibits cell death at a late (postmitochondrial) step in the death pathway was supported by the study of Chau et al. (2000). Using a yeast 2-hybrid screen of a B-cell cDNA library, they identified a novel apoptosis inhibitor, which they termed AVEN (derived from 'Aventine,' a Roman stronghold), that binds to both BCLXL and the caspase regulator APAF1 (602233). The AVEN gene encodes a 362-amino acid protein and is conserved in other mammalian species. Northern blot analysis detected a 1.7-kb AVEN transcript in all adult tissues tested, with highest expression in heart, skeletal muscle, kidney, liver, pancreas, and testis; a number of cell lines also expressed AVEN. Only those mutants of BCLXL that retained their antiapoptotic activity were capable of binding AVEN. AVEN was shown to interfere with the ability of APAF1 to self-associate, suggesting that AVEN impairs APAF1-mediated activation of caspases. Consistent with this idea, AVEN inhibited the proteolytic activation of caspases in a cell-free extract and suppressed apoptosis induced by APAF1 plus caspase-9 (CASP9; 602234). Thus, AVEN represents a novel class of cell death regulator.
By genomic sequencing, Chau et al. (2000) mapped the AVEN gene to chromosome 15.
Chau, B. N., Cheng, E. H.-Y., Kerr, D. A., Hardwick, J. M. Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1. Molec. Cell 6: 31-40, 2000. [PubMed: 10949025]