XB-ART-43778
PLoS One
January 1, 2011;
6
(8):
e23672.
Unfertilized Xenopus eggs die by Bad-dependent apoptosis under the control of Cdk1 and JNK.
Abstract
Ovulated eggs possess maternal apoptotic execution machinery that is inhibited for a limited time. The fertilized eggs switch off this time bomb whereas aged unfertilized eggs and parthenogenetically activated eggs fail to stop the timer and die. To investigate the nature of the molecular clock that triggers the egg decision of committing suicide, we introduce here Xenopus eggs as an in vivo system for studying the death of unfertilized eggs. We report that after ovulation, a number of eggs remains in the female body where they die by apoptosis. Similarly, ovulated unfertilized eggs recovered in the external medium die within 72 h. We showed that the death process depends on both cytochrome c release and caspase activation. The apoptotic machinery is turned on during meiotic maturation, before fertilization. The death pathway is independent of ERK but relies on activating Bad phosphorylation through the control of both kinases Cdk1 and JNK. In conclusion, the default fate of an unfertilized Xenopus egg is to die by a mitochondrial dependent apoptosis activated during meiotic maturation.
PubMed ID: 21858202
PMC ID: PMC3156807
Article link: PLoS One
Species referenced: Xenopus
Genes referenced: bax bcl2l1 casp1 casp2 casp3.2 casp8 casp9 ccnb2 cdk1 clock fh h2bc21 kcnip4 mapk1 mapk8 mcl1 mos wwc2
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References [+] :
Antignani,
How do Bax and Bak lead to permeabilization of the outer mitochondrial membrane?
2006, Pubmed
Antignani,
How do Bax and Bak lead to permeabilization of the outer mitochondrial membrane?
2006,
Pubmed
Austin, Ageing and reproduction: post-ovulatory deterioration of the egg. 1970, Pubmed
Ayllón, Protein phosphatase 1alpha is a Ras-activated Bad phosphatase that regulates interleukin-2 deprivation-induced apoptosis. 2000, Pubmed
Bagowski, c-Jun N-terminal kinase activation in Xenopus laevis eggs and embryos. A possible non-genomic role for the JNK signaling pathway. 2001, Pubmed , Xenbase
Bennett, SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. 2001, Pubmed
Bhakar, Apoptosis induced by p75NTR overexpression requires Jun kinase-dependent phosphorylation of Bad. 2003, Pubmed
Brun, DNA topoisomerase I from mitochondria of Xenopus laevis oocytes. 1981, Pubmed , Xenbase
Budihardjo, Biochemical pathways of caspase activation during apoptosis. 2000, Pubmed
Cheung, Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase. 2003, Pubmed
Chiang, Protein phosphatase 2A dephosphorylation of phosphoserine 112 plays the gatekeeper role for BAD-mediated apoptosis. 2003, Pubmed
Coen, Xenopus Bcl-X(L) selectively protects Rohon-Beard neurons from metamorphic degeneration. 2001, Pubmed , Xenbase
De Smedt, Thr-161 phosphorylation of monomeric Cdc2. Regulation by protein phosphatase 2C in Xenopus oocytes. 2002, Pubmed , Xenbase
Deming, Study of apoptosis in vitro using the Xenopus egg extract reconstitution system. 2006, Pubmed , Xenbase
Domingos, Pathways regulating apoptosis during patterning and development. 2007, Pubmed
Donovan, JNK phosphorylation and activation of BAD couples the stress-activated signaling pathway to the cell death machinery. 2002, Pubmed
Dupré, Mos is not required for the initiation of meiotic maturation in Xenopus oocytes. 2002, Pubmed , Xenbase
Elmore, Apoptosis: a review of programmed cell death. 2007, Pubmed
Favata, Identification of a novel inhibitor of mitogen-activated protein kinase kinase. 1998, Pubmed
Frank-Vaillant, Two distinct mechanisms control the accumulation of cyclin B1 and Mos in Xenopus oocytes in response to progesterone. 1999, Pubmed , Xenbase
Fujino, DNA fragmentation of oocytes in aged mice. 1996, Pubmed
Golsteyn, Cdk1 and Cdk2 complexes (cyclin dependent kinases) in apoptosis: a role beyond the cell cycle. 2004, Pubmed
Goris, Okadaic acid, a specific protein phosphatase inhibitor, induces maturation and MPF formation in Xenopus laevis oocytes. 1989, Pubmed , Xenbase
Gross, BCL-2 family members and the mitochondria in apoptosis. 1999, Pubmed
Gross, The critical role of the MAP kinase pathway in meiosis II in Xenopus oocytes is mediated by p90(Rsk). 2000, Pubmed , Xenbase
Haccard, Oocyte maturation, Mos and cyclins--a matter of synthesis: two functionally redundant ways to induce meiotic maturation. 2006, Pubmed
Hans, Histone H3 phosphorylation and cell division. 2001, Pubmed
Hara, A cytoplasmic clock with the same period as the division cycle in Xenopus eggs. 1980, Pubmed , Xenbase
Huchon, Protein phosphatase-1 is involved in Xenopus oocyte maturation. 1982, Pubmed , Xenbase
Jessus, Fertilization: calcium's double punch. 2007, Pubmed , Xenbase
Jessus, Tyrosine phosphorylation of p34cdc2 and p42 during meiotic maturation of Xenopus oocyte. Antagonistic action of okadaic acid and 6-DMAP. 1991, Pubmed , Xenbase
Junttila, Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival. 2008, Pubmed
Kluck, The pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol. 1999, Pubmed , Xenbase
Klumpp, Protein phosphatase type 2C dephosphorylates BAD. 2003, Pubmed
Konishi, Cdc2 phosphorylation of BAD links the cell cycle to the cell death machinery. 2002, Pubmed
Laemmli, Cleavage of structural proteins during the assembly of the head of bacteriophage T4. 1970, Pubmed
Lane, Apoptotic cleavage of cytoplasmic dynein intermediate chain and p150(Glued) stops dynein-dependent membrane motility. 2001, Pubmed , Xenbase
Lei, The Bax subfamily of Bcl2-related proteins is essential for apoptotic signal transduction by c-Jun NH(2)-terminal kinase. 2002, Pubmed
Lei, JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. 2003, Pubmed
Lin, Activation of the JNK signaling pathway: breaking the brake on apoptosis. 2002, Pubmed
Mochida, Regulated activity of PP2A-B55 delta is crucial for controlling entry into and exit from mitosis in Xenopus egg extracts. 2009, Pubmed , Xenbase
Mood, Contribution of JNK, Mek, Mos and PI-3K signaling to GVBD in Xenopus oocytes. 2004, Pubmed , Xenbase
Morita, Targeted expression of Bcl-2 in mouse oocytes inhibits ovarian follicle atresia and prevents spontaneous and chemotherapy-induced oocyte apoptosis in vitro. 1999, Pubmed
Morita, Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. 2000, Pubmed
Newmeyer, Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria. 1994, Pubmed , Xenbase
Nutt, Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. 2005, Pubmed , Xenbase
Nutt, Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2. 2009, Pubmed , Xenbase
Perez, Cumulus cells are required for the increased apoptotic potential in oocytes of aged mice. 1998, Pubmed
Perez, Fragmentation and death (a.k.a. apoptosis) of ovulated oocytes. 1999, Pubmed
Perez, Mitochondria and the death of oocytes. 2000, Pubmed
Porter, Emerging roles of caspase-3 in apoptosis. 1999, Pubmed
Rowe, Apoptosis of tail muscle during amphibian metamorphosis involves a caspase 9-dependent mechanism. 2005, Pubmed , Xenbase
Sadler, MAP kinases regulate unfertilized egg apoptosis and fertilization suppresses death via Ca2+ signaling. 2004, Pubmed
Saitoh, Pro-apoptotic activity and mono-/diubiquitylation of Xenopus Bid in egg extracts. 2009, Pubmed , Xenbase
Sasaki, Fertilization blocks apoptosis of starfish eggs by inactivation of the MAP kinase pathway. 2001, Pubmed
Tarín, Long-term effects of postovulatory aging of mouse oocytes on offspring: a two-generational study. 1999, Pubmed
Tarín, Consequences on offspring of abnormal function in ageing gametes. 2000, Pubmed
Tashker, Post-cytochrome C protection from apoptosis conferred by a MAPK pathway in Xenopus egg extracts. 2002, Pubmed , Xenbase
Tsuchiya, Apoptosis-inhibiting activities of BIR family proteins in Xenopus egg extracts. 2005, Pubmed , Xenbase
Tsuchiya, Anti-apoptotic activity and proteasome-mediated degradation of Xenopus Mcl-1 protein in egg extracts. 2011, Pubmed , Xenbase
Turk, Protease signalling in cell death: caspases versus cysteine cathepsins. 2007, Pubmed
Walker, Multiple roles for protein phosphatase 1 in regulating the Xenopus early embryonic cell cycle. 1992, Pubmed , Xenbase
Yu, JNK suppresses apoptosis via phosphorylation of the proapoptotic Bcl-2 family protein BAD. 2004, Pubmed
Yuce, Postmeiotic unfertilized starfish eggs die by apoptosis. 2001, Pubmed
Zha, Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L) 1997, Pubmed
Zha, BH3 domain of BAD is required for heterodimerization with BCL-XL and pro-apoptotic activity. 1997, Pubmed
Zhang, BAD Ser128 is not phosphorylated by c-Jun NH2-terminal kinase for promoting apoptosis. 2005, Pubmed
Zhou, Antiapoptotic role for ornithine decarboxylase during oocyte maturation. 2009, Pubmed , Xenbase
Austin, Ageing and reproduction: post-ovulatory deterioration of the egg. 1970, Pubmed
Ayllón, Protein phosphatase 1alpha is a Ras-activated Bad phosphatase that regulates interleukin-2 deprivation-induced apoptosis. 2000, Pubmed
Bagowski, c-Jun N-terminal kinase activation in Xenopus laevis eggs and embryos. A possible non-genomic role for the JNK signaling pathway. 2001, Pubmed , Xenbase
Bennett, SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. 2001, Pubmed
Bhakar, Apoptosis induced by p75NTR overexpression requires Jun kinase-dependent phosphorylation of Bad. 2003, Pubmed
Brun, DNA topoisomerase I from mitochondria of Xenopus laevis oocytes. 1981, Pubmed , Xenbase
Budihardjo, Biochemical pathways of caspase activation during apoptosis. 2000, Pubmed
Cheung, Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase. 2003, Pubmed
Chiang, Protein phosphatase 2A dephosphorylation of phosphoserine 112 plays the gatekeeper role for BAD-mediated apoptosis. 2003, Pubmed
Coen, Xenopus Bcl-X(L) selectively protects Rohon-Beard neurons from metamorphic degeneration. 2001, Pubmed , Xenbase
De Smedt, Thr-161 phosphorylation of monomeric Cdc2. Regulation by protein phosphatase 2C in Xenopus oocytes. 2002, Pubmed , Xenbase
Deming, Study of apoptosis in vitro using the Xenopus egg extract reconstitution system. 2006, Pubmed , Xenbase
Domingos, Pathways regulating apoptosis during patterning and development. 2007, Pubmed
Donovan, JNK phosphorylation and activation of BAD couples the stress-activated signaling pathway to the cell death machinery. 2002, Pubmed
Dupré, Mos is not required for the initiation of meiotic maturation in Xenopus oocytes. 2002, Pubmed , Xenbase
Elmore, Apoptosis: a review of programmed cell death. 2007, Pubmed
Favata, Identification of a novel inhibitor of mitogen-activated protein kinase kinase. 1998, Pubmed
Frank-Vaillant, Two distinct mechanisms control the accumulation of cyclin B1 and Mos in Xenopus oocytes in response to progesterone. 1999, Pubmed , Xenbase
Fujino, DNA fragmentation of oocytes in aged mice. 1996, Pubmed
Golsteyn, Cdk1 and Cdk2 complexes (cyclin dependent kinases) in apoptosis: a role beyond the cell cycle. 2004, Pubmed
Goris, Okadaic acid, a specific protein phosphatase inhibitor, induces maturation and MPF formation in Xenopus laevis oocytes. 1989, Pubmed , Xenbase
Gross, BCL-2 family members and the mitochondria in apoptosis. 1999, Pubmed
Gross, The critical role of the MAP kinase pathway in meiosis II in Xenopus oocytes is mediated by p90(Rsk). 2000, Pubmed , Xenbase
Haccard, Oocyte maturation, Mos and cyclins--a matter of synthesis: two functionally redundant ways to induce meiotic maturation. 2006, Pubmed
Hans, Histone H3 phosphorylation and cell division. 2001, Pubmed
Hara, A cytoplasmic clock with the same period as the division cycle in Xenopus eggs. 1980, Pubmed , Xenbase
Huchon, Protein phosphatase-1 is involved in Xenopus oocyte maturation. 1982, Pubmed , Xenbase
Jessus, Fertilization: calcium's double punch. 2007, Pubmed , Xenbase
Jessus, Tyrosine phosphorylation of p34cdc2 and p42 during meiotic maturation of Xenopus oocyte. Antagonistic action of okadaic acid and 6-DMAP. 1991, Pubmed , Xenbase
Junttila, Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival. 2008, Pubmed
Kluck, The pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol. 1999, Pubmed , Xenbase
Klumpp, Protein phosphatase type 2C dephosphorylates BAD. 2003, Pubmed
Konishi, Cdc2 phosphorylation of BAD links the cell cycle to the cell death machinery. 2002, Pubmed
Laemmli, Cleavage of structural proteins during the assembly of the head of bacteriophage T4. 1970, Pubmed
Lane, Apoptotic cleavage of cytoplasmic dynein intermediate chain and p150(Glued) stops dynein-dependent membrane motility. 2001, Pubmed , Xenbase
Lei, The Bax subfamily of Bcl2-related proteins is essential for apoptotic signal transduction by c-Jun NH(2)-terminal kinase. 2002, Pubmed
Lei, JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. 2003, Pubmed
Lin, Activation of the JNK signaling pathway: breaking the brake on apoptosis. 2002, Pubmed
Mochida, Regulated activity of PP2A-B55 delta is crucial for controlling entry into and exit from mitosis in Xenopus egg extracts. 2009, Pubmed , Xenbase
Mood, Contribution of JNK, Mek, Mos and PI-3K signaling to GVBD in Xenopus oocytes. 2004, Pubmed , Xenbase
Morita, Targeted expression of Bcl-2 in mouse oocytes inhibits ovarian follicle atresia and prevents spontaneous and chemotherapy-induced oocyte apoptosis in vitro. 1999, Pubmed
Morita, Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. 2000, Pubmed
Newmeyer, Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria. 1994, Pubmed , Xenbase
Nutt, Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. 2005, Pubmed , Xenbase
Nutt, Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2. 2009, Pubmed , Xenbase
Perez, Cumulus cells are required for the increased apoptotic potential in oocytes of aged mice. 1998, Pubmed
Perez, Fragmentation and death (a.k.a. apoptosis) of ovulated oocytes. 1999, Pubmed
Perez, Mitochondria and the death of oocytes. 2000, Pubmed
Porter, Emerging roles of caspase-3 in apoptosis. 1999, Pubmed
Rowe, Apoptosis of tail muscle during amphibian metamorphosis involves a caspase 9-dependent mechanism. 2005, Pubmed , Xenbase
Sadler, MAP kinases regulate unfertilized egg apoptosis and fertilization suppresses death via Ca2+ signaling. 2004, Pubmed
Saitoh, Pro-apoptotic activity and mono-/diubiquitylation of Xenopus Bid in egg extracts. 2009, Pubmed , Xenbase
Sasaki, Fertilization blocks apoptosis of starfish eggs by inactivation of the MAP kinase pathway. 2001, Pubmed
Tarín, Long-term effects of postovulatory aging of mouse oocytes on offspring: a two-generational study. 1999, Pubmed
Tarín, Consequences on offspring of abnormal function in ageing gametes. 2000, Pubmed
Tashker, Post-cytochrome C protection from apoptosis conferred by a MAPK pathway in Xenopus egg extracts. 2002, Pubmed , Xenbase
Tsuchiya, Apoptosis-inhibiting activities of BIR family proteins in Xenopus egg extracts. 2005, Pubmed , Xenbase
Tsuchiya, Anti-apoptotic activity and proteasome-mediated degradation of Xenopus Mcl-1 protein in egg extracts. 2011, Pubmed , Xenbase
Turk, Protease signalling in cell death: caspases versus cysteine cathepsins. 2007, Pubmed
Walker, Multiple roles for protein phosphatase 1 in regulating the Xenopus early embryonic cell cycle. 1992, Pubmed , Xenbase
Yu, JNK suppresses apoptosis via phosphorylation of the proapoptotic Bcl-2 family protein BAD. 2004, Pubmed
Yuce, Postmeiotic unfertilized starfish eggs die by apoptosis. 2001, Pubmed
Zha, Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L) 1997, Pubmed
Zha, BH3 domain of BAD is required for heterodimerization with BCL-XL and pro-apoptotic activity. 1997, Pubmed
Zhang, BAD Ser128 is not phosphorylated by c-Jun NH2-terminal kinase for promoting apoptosis. 2005, Pubmed
Zhou, Antiapoptotic role for ornithine decarboxylase during oocyte maturation. 2009, Pubmed , Xenbase