Aven blocks DNA damage-induced apoptosis by stabilising Bcl-xL

Kütük, Özgür; Temel, Şehime Gülsün; Tolunay, Şahsine; Başağa, Hüveyda

doi:10.1016/j.ejca.2010.06.011

Cited by 32 publications

(34 citation statements)

References 45 publications

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“…These findings suggest that BCL-x L and AVEN act synergistically to prevent apoptosis, such that when Bcl-xL is depleted the pro-survival activity of AVEN is abolished. A similar interaction has previously been reported in breast cancer cells treated with DNA-damaging reagents [25]. Recent analysis of the AVEN protein sequence has identified a BCL2 homology 3 (BH3) domain, indicating that AVEN is a novel member of the BCL2 family of apoptotic regulators [52].…”

Section: P4 Signalling and Apoptosismentioning

confidence: 70%

“…AVEN is known to play a role in male and female germ cell development; downregulation of AVEN was associated with incomplete spermatogenesis in mice [18] and Vasa-homolog-deficient mice, which display abnormal spermatogenesis, fail to express AVEN [19], while over expression of human AVEN mRNA in Xenopus laevis oocytes delays P4 induced meiotic maturation [20]. AVEN protein has also been shown to inhibit the mitochondrial apoptosis pathway by binding to and inhibiting the self-association of pro-apoptotic APAF-1 [21,22], as well as binding to and enhancing anti-apoptotic BCL-x L activity [21,[23][24][25]. However, AVEN can induce apoptosis in cells with high levels of DNA damage, while promoting the recovery of cells with lower levels of DNA damage.…”

Section: Introductionmentioning

confidence: 96%

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Progesterone Regulation of AVEN Protects Bovine Oocytes from Apoptosis During Meiotic Maturation1

O'Shea

Hensey

Fair

2013

Biology of Reproduction

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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.

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Section: P4 Signalling and Apoptosismentioning

confidence: 70%

Section: Introductionmentioning

confidence: 96%

Progesterone Regulation of AVEN Protects Bovine Oocytes from Apoptosis During Meiotic Maturation1

O'Shea

Hensey

Fair

2013

Biology of Reproduction

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“…Although initially identified in a yeast two-hybrid screen for Bcl-x L -interacting proteins, 13 Aven has also been found to bind to Apaf-1, thereby interfering with Apaf-1 self-association during apoptosome assembly. Whether the interaction of Aven with Bcl-x L contributes to its anti-apoptotic activity 14 or it is in fact dispensable 13 remains an open question.…”

mentioning

confidence: 99%

The Apaf-1-binding protein Aven is cleaved by Cathepsin D to unleash its anti-apoptotic potential

et al. 2012

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The anti-apoptotic molecule Aven was originally identified in a yeast two-hybrid screen for Bcl-x L -interacting proteins and has also been found to bind Apaf-1, thereby interfering with Apaf-1 self-association during apoptosome assembly. Aven is expressed in a wide variety of adult tissues and cell lines, and there is increasing evidence that its overexpression correlates with tumorigenesis, particularly in acute leukemias. The mechanism by which the anti-apoptotic activity of Aven is regulated remains poorly understood. Here we shed light on this issue by demonstrating that proteolytic removal of an inhibitory N-terminal Aven domain is necessary to activate the anti-apoptotic potential of the molecule. Furthermore, we identify Cathepsin D (CathD) as the protease responsible for Aven cleavage. On the basis of our results, we propose a model of Aven activation by which its N-terminal inhibitory domain is removed by CathD-mediated proteolysis, thereby unleashing its cytoprotective function.

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“…However, disturbance of this delicate equilibrium toward increased germ cell apoptosis can cause male factor infertility (1,22). Aven has been shown to be an inhibitor of apoptosis in several cell types (13,(23)(24)(25)(26) by enhancing Bcl-xL antiapoptotic activity and inhibiting Apaf-1 self-assembly (13). A possible role for Aven in the regulation of testicular apoptosis had not yet been studied, although Vasa-homologdeficient mice displaying defective spermatogenesis fail to express Aven (14).…”

Section: Discussionmentioning

confidence: 97%

Apoptosis-inhibitor Aven is downregulated in defective spermatogenesis and a novel estrogen target gene in mammalian testis

Laurentino

Gonçalves

Cavaco

et al. 2011

Fertility and Sterility

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Aven blocks DNA damage-induced apoptosis by stabilising Bcl-xL

Cited by 32 publications

References 45 publications

Progesterone Regulation of AVEN Protects Bovine Oocytes from Apoptosis During Meiotic Maturation1

Progesterone Regulation of AVEN Protects Bovine Oocytes from Apoptosis During Meiotic Maturation1

The Apaf-1-binding protein Aven is cleaved by Cathepsin D to unleash its anti-apoptotic potential

Apoptosis-inhibitor Aven is downregulated in defective spermatogenesis and a novel estrogen target gene in mammalian testis

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