XLX is an IAP family member regulated by phosphorylation during meiosis

Greenwood, Jessica; Gautier, Jean‐Charles

doi:10.1038/sj.cdd.4402031

Cited by 5 publications

(4 citation statements)

References 36 publications

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“…GVBD results in a sharply demarcated loss of pigment in the animal pole, which, although distinct from apoptotic morphology, renders visual determination of whether a meiotic oocyte (post-GVBD) is undergoing apoptotic death challenging (Figure 5a). Using cell-free systems, we and others have reported that a meiotic state (M-phase) engenders resistance to cytochrome c -induced caspase activation24,25. A comparison of IRDye fluorescence in immature and mature (post-GVBD) oocytes microinjected with cytochrome c confirmed that sensitivity to cytochrome c decreases with maturation (Figure 5b).…”

Section: Resultssupporting

confidence: 57%

Features of programmed cell death in intact Xenopus oocytes and early embryos revealed by near-infrared fluorescence and real-time monitoring

2009

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Factors influencing apoptosis of vertebrate eggs and early embryos have been studied in cell-free systems and in intact embryos by analyzing individual apoptotic regulators or caspase activation in static samples. Described here is a novel method for monitoring caspase activity in living Xenopus oocytes and early embryos. The approach, utilizing microinjection of a near-infrared caspase substrate that emits fluorescence only after its proteolytic cleavage by active effector caspases, has enabled the elucidation of otherwise cryptic aspects of apoptotic regulation. In particular, we demonstrate that brief caspase activity (ten minutes) is sufficient to cause apoptotic death in this system. We illustrate a cytochrome c dose threshold in the oocyte, which is lowered by Smac, a protein that binds thereby neutralizing inhibitor of apoptosis proteins. We show that meiotic oocytes develop resistance to cytochrome c, and that eventual death of oocytes arrested in meiosis is caspase-independent. Finally, data acquired through imaging caspase activity in the Xenopus embryo suggests that apoptosis in very early development is not cell-autonomous. These studies both validate this assay as a useful tool for apoptosis research and reveal subtleties in the cell death program during early development. Moreover, this method offers a potentially valuable screening modality for identifying novel apoptotic regulators.

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Section: Resultssupporting

confidence: 57%

Features of programmed cell death in intact Xenopus oocytes and early embryos revealed by near-infrared fluorescence and real-time monitoring

2009

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“…Among the other apoptotic factors, the inhibitor of apoptosis (IAP) family of proteins containing the highly conserved baculoviral IAP repeat (BIR) are known to inhibit apoptosis, in some cases, through direct binding of caspases. XLX and XIAP, the X. laevis BIR family proteins, have been shown to inhibit the apoptotic process in the cell-free system of X. laevis egg extract [102, 103]. However, their involvement in metamorphosis as well as TH dependency remains to be determined.…”

Section: Apoptotic Factors Regulated By Thmentioning

confidence: 99%

Apoptosis in amphibian organs during metamorphosis

2009

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During amphibian metamorphosis, the larval tissues/organs rapidly degenerate to adapt from the aquatic to the terrestrial life. At the cellular level, a large quantity of apoptosis occurs in a spatiotemporally-regulated fashion in different organs to ensure timely removal of larval organs/tissues and the development of adult ones for the survival of the individuals. Thus, amphibian metamorphosis provides us a good opportunity to understand the mechanisms regulating apoptosis. To investigate this process at the molecular level, a number of thyroid hormone (TH) response genes have been isolated from several organs of Xenopus laevis tadpoles and their expression and functional analyses are now in progress using modern molecular and genetic technologies. In this review, we will first summarize when and where apoptosis occurs in typical larva-specific and larval-to-adult remodeling amphibian organs to highlight that the timing of apoptosis is different in different tissues/organs, even though all are induced by the same circulating TH. Next, to discuss how TH spatiotemporally regulates the apoptosis, we will focus on apoptosis of the X. laevis small intestine, one of the best characterized remodeling organs. Functional studies of TH response genes using transgenic frogs and culture techniques have shown that apoptosis of larval epithelial cells can be induced by TH either cell-autonomously or indirectly through interactions with extracellular matrix (ECM) components of the underlying basal lamina. Here, we propose that multiple intra- and extracellular apoptotic pathways are coordinately controlled by TH to ensure massive but well-organized apoptosis, which is essential for the proper progression of amphibian metamorphosis.

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“…4, 6XHis-xE-IAP). These results indicate that the stabilized xXIAP and xEIAP/XLX could also contribute to the inhibition of apoptosis in acid-treated egg extracts [18,19]. Altogether, multiple apoptosis-regulating pathways were affected by the addition of acidic solutions to egg extracts.…”

Section: Resultsmentioning

confidence: 81%

Inhibition of apoptosis by ascorbic and dehydroascorbic acids in Xenopus egg extracts

Saitoh

Tsuchiya

Kinoshita

et al. 2008

Reprod Medicine & Biology

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Purpose The viability of mammalian eggs after ovulation is reported to be improved by the presence of ascorbic acid in the culture medium. However, the pro-survival mechanisms of ascorbic acid are poorly understood. The molecular pathways of apoptosis are evolutionarily conserved among animal species, and Xenopus eggs are technically and ethically more suitable for biochemical analyses than mammalian eggs. We used Xenopus egg cytoplasmic extracts to examine the direct intracellular effects of ascorbic acid. Methods Incubation of egg extracts for more than 4 h induces the spontaneous release of cytochrome c from mitochondria. This event triggers the activation of caspases, cleavage of substrate proteins, and execution of apoptosis. Multiple signal transduction pathways including proteolysis and protein phosphorylation are also involved in this process. We examined whether any of these events might be inhibited by the addition of ascorbic acid. Results Ascorbic acid showed no effect against cytochrome c release, but prevented caspase activation and substrate cleavage. Ascorbic acid also blocked the proteolysis of apoptosis inhibitor proteins and the dephosphorylation of p42 MAP kinase. However, dehydroascorbic acid (oxidized form of ascorbic acid) and acetate (unrelated acid) were equally effective, indicating that these effects were primarily due to their acidity. In addition, dehydroascorbic acid inhibited caspase activities directly in vitro. Conclusions The anti-apoptotic effect of ascorbic acid in Xenopus egg extracts is mainly due to cytoplasmic acidification rather than its intracellular antioxidant activity. Instead, oxidative conversion of ascorbic acid into dehydroascorbic acid may inhibit apoptosis through the inhibition of caspases.

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XLX is an IAP family member regulated by phosphorylation during meiosis

Cited by 5 publications

References 36 publications

Features of programmed cell death in intact Xenopus oocytes and early embryos revealed by near-infrared fluorescence and real-time monitoring

Features of programmed cell death in intact Xenopus oocytes and early embryos revealed by near-infrared fluorescence and real-time monitoring

Apoptosis in amphibian organs during metamorphosis

Inhibition of apoptosis by ascorbic and dehydroascorbic acids in Xenopus egg extracts

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