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Ovarian Kaleidoscope Database (OKdb)

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apoptosis and caspase activation inhibitor OKDB#: 4940
 Symbols: AVEN Species: human
 Synonyms: PDCD12  Locus: 15q14 in Homo sapiens


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General Comment Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1. Chau BN 2000 et al. Bcl-x(L), an antiapoptotic Bcl-2 family member, is postulated to function at multiple stages in the cell death pathway. The possibility that Bcl-x(L) inhibits cell death at a late (postmitochondrial) step in the death pathway is supported by this report of a novel apoptosis inhibitor, Aven, which binds to both Bcl-x(L) and the caspase regulator, Apaf-1. Identified in a yeast two-hybrid screen, Aven is broadly expressed and is conserved in other mammalian species. Only those mutants of Bcl-x(L)that retain their antiapoptotic activity are capable of binding Aven. Aven interferes with the ability of Apaf-1 to self-associate, suggesting that Aven impairs Apaf-1-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 Apaf-1 plus caspase-9. Thus, Aven represents a new class of cell death regulator. /////////////////////////

General function Anti-apoptotic
Comment
Cellular localization Cytoplasmic
Comment
Ovarian function Follicle atresia, Oocyte maturation, Early embryo development
Comment Expression of granulosa cell microRNAs, AVEN and ATRX are associated with human blastocyst development. O'Doherty AM et al. (2018) A greater understanding of the key molecules associated with embryo development during human assisted reproduction is imperative for the development of advanced diagnostics. Previous studies have shown that follicular microRNAs (miRNAs) are reliable markers of polycystic ovarian syndrome (PCOS). Leveraging the utility of miRNAs in PCOS, the aim of this study was to identify miRNAs in human granulosa cells that may be indicative of blastocyst development. Granulosa cells and oocytes were collected from the first follicle aspirated from patients undergoing oocyte retrieval for in-vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI). The development of isolated oocytes was recorded and granulosa cell samples in this study were separated as follows; Group 1-BLAST: granulosa cells from follicles containing an oocyte that fertilised and developed into a blastocyst and Group 2-FERT: granulosa cells from oocytes that fertilised but failed to reach blastocyst. A panel of 84 miRNAs, related to development and cellular differentiation, were assessed between the two groups using a miScript PCR array. Fourteen miRNAs and one snoRNA were differentially expressed between the groups. Additionally, two downstream candidate protein biomarkers, ATRX and AVEN, were also found to be differentially expressed between the groups. The findings of this pilot study reveal follicular abnormalities on a molecular level which may affect oocyte competence and its potential to develop successfully as an embryo. We encourage additional studies to confirm and expand on our findings and to determine the usefulness of granulosa-borne miRNAs, ATRX and AVEN as biomarkers. This article is protected by copyright. All rights reserved.////////////////// Progesterone Regulation of AVEN Protects Bovine Oocytes from Apoptosis During Meiotic Maturation. O'Shea LC 2013 et al. Inhibition of progesterone (P4) synthesis by cumulus cells during bovine in vitro oocyte maturation (IVM) causes a decrease in subsequent embryo development, indicating that P4 intracellular signaling within the cumulus oocyte complex (COC) is important for oocyte developmental competence. The aim of the present study was to further elucidate, on a protein level, the downstream signaling pathway involved in P4 regulation of oocyte developmental competence. COCs were subjected to IVM for 24 h in the presence or absence of trilostane, aglepristone or promegestone (R5020). These altered IVM conditions resulted in dynamic changes in protein expression of the progesterone receptors and the cell death regulated proteins, AVEN, BCL-xL and active Caspase-3. In addition, AVEN protein localization, Caspase-3 activation and mitochondrial distribution were studied by immunofluorescence. Inhibition of progesterone synthesis (Trilostane treatment) resulted in changes in AVEN localization within the COC, corresponding to Caspase-3 activation and altered mitochondrial distribution. AVEN was also found to bind BCL-xL in COCs, but this interaction was lost following treatment with Trilostane. /////////////////////////
Expression regulated by Steroids, P4
Comment
Ovarian localization Oocyte, Cumulus, Granulosa
Comment
Follicle stages
Comment
Phenotypes
Mutations 0 mutations
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Phenotypes and GWAS show phenotypes and GWAS
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created: Nov. 4, 2013, 11:24 a.m. by: hsueh   email:
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last update: April 26, 2018, 9:14 a.m. by: hsueh    email:



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