Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis

Relaix, Frédéric; Wei, Xiao; Li, Wei; Pan, Jianjing; Lin, Yunzhi; Bowtell, David D.L.; Sassoon, David; Wu, Xiangwei

doi:10.1073/pnas.040378897

Cited by 160 publications

(174 citation statements)

References 23 publications

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“…RNA expression peaked at 7 h post-treatment and decreased later on ( Figure 6a, and not shown). In addition, the BH3-protein PUMA, 17,18 the zinc finger protein Peg3, 69 and the p53 target gene p21/WAF1 70 were induced in a p53-dependent manner (Figure 6a). In contrast, the expression of proapoptotic Bak, which acts at the same level as Bax during stressinduced apoptosis in MEF, 71,72 remained unchanged following etoposide treatment (Figure 6a).…”

Section: Resultsmentioning

confidence: 98%

p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation

et al. 2003

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The mechanism of p53-dependent apoptosis is still only partly defined. Using early-passage embryonic fibroblasts (MEF) from wild-type (wt), p53 À/À and bax À/À mice, we observe a p53-dependent translocation of Bax to the mitochondria and a release of mitochondrial Cytochrome c during stress-induced apoptosis. These events proceed independent of zVADinhibitable caspase activation, are not prevented by dominant negative FADD (DN-FADD), but are negatively regulated by Mdm-2. Bcl-x L expression prevents the release of mitochondrial Cytochrome c and apoptosis, but not Bax translocation. At a single-cell level, enforced expression of p53 is sufficient to induce Bax translocation and Cytochrome c release. Real-time RT-PCR analysis reveals a significant induction of RNA expression of Noxa and Bax in p53 +/+ , but not in p53 À/À MEF. Noxa protein expression becomes detectable prior to Bax translocation, and downregulation of endogenous Noxa by RNA interference protects wt MEF against p53-dependent apoptosis. Hence, in oncogene-expressing MEF p53 induces apoptosis by BH3 protein-dependent caspase activation.

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Section: Resultsmentioning

confidence: 98%

p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation

et al. 2003

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“…The murine Siah-1b was reported to be a direct transcriptional target of p53 (Fiucci et al, 2004). Some studies have also suggested that human Siah-1 may act as a downstream effector of p53 (Hu et al, 1997a;Matsuzawa et al, 1998;Roperch et al, 1999;Relaix et al, 2000;Liu et al, 2001;Maeda et al, 2002). However, the mechanism by which p53 induces human Siah-1 gene is still unclear.…”

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confidence: 92%

Siah-1L, a novel transcript variant belonging to the human Siah family of proteins, regulates β-catenin activity in a p53-dependent manner

et al. 2004

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b-Catenin is a potent oncogenic protein whose cytoplasmic accumulation is a frequent event in cancer cells. The level of b-catenin is regulated by two mechanisms: the adenomatous polyposis coli/Axin/glycogen synthase kinase 3b-dependent degradation pathway and the Siah-1/ Siah interacting protein/Ebi-mediated degradation pathway. In this study, we have investigated the functional significance of p53-inducible human Siah-family protein expression in the regulation of b-catenin activity. We show here by reverse-transcriptase polymerase chain reaction that two mRNA transcripts, designated human Siah-1 and Siah-1L, are generated from the human Siah-1 locus. Interestingly, the expression of Siah-1L was upregulated by p53, whereas human Siah-1 expression was constant. Furthermore, introduction of exogenous Siah-1L protein downregulated b-catenin protein and promoted apoptosis induced by anticancer drugs in cancer cells that lack endogenous p53. Thus, Siah-1L represents a new member of the human Siah family that is induced in response to p53 and plays an important role in the regulation of b-catenin activity in tumor cells. These findings also suggest new strategies for restoring tumor suppressive pathways lost in cancer cells that have suffered p53 inactivation.

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“…This suggested a deficit in the neurobiological control of lactation, and investigations demonstrated a reduced number of oxytocin-positive neurons in the hypothalamus of Peg3 mutant females (Li et al 1999). Given the central role played by oxytocin in both maternal behaviour and milk letdown, the indication is that this is the neurobiological pathway via which Peg3 is exerting an effect (Keverne 2001), an idea that sits nicely with its involvement in the tumour necrosis factor signalling pathway affecting NFkB phosphorylation, apoptosis and cell survival (Relaix et al 1998(Relaix et al , 2000.…”

Section: The Pre-weaning Period and Mother-offspring Bondingmentioning

confidence: 99%

Genomic imprinting and the social brain

Isles

Davies

Wilkinson

2006

Phil. Trans. R. Soc. B

109

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Genomic imprinting refers to the parent-of-origin-specific epigenetic marking of a number of genes. This epigenetic mark leads to a bias in expression between maternally and paternally inherited imprinted genes, that in some cases results in monoallelic expression from one parental allele. Genomic imprinting is often thought to have evolved as a consequence of the intragenomic conflict between the parental alleles that occurs whenever there is an asymmetry of relatedness. The two main examples of asymmetry of relatedness are when there is partiality of parental investment in offspring (as is the case for placental mammals, where there is also the possibility of extended postnatal care by one parent), and in social groups where there is a sex-biased dispersal. From this evolutionary starting point, it is predicted that, at the behavioural level, imprinted genes will influence what can broadly be termed bonding and social behaviour. We examine the animal and human literature for examples of imprinted genes mediating these behaviours, and divide them into two general classes. Firstly, mother-offspring interactions (suckling, attachment and maternal behaviours) that are predicted to occur when partiality in parental investment in early postnatal offspring occurs; and secondly, adult social interactions, when there is an asymmetry of relatedness in social groups. Finally, we return to the evolutionary theory and examine whether there is a pattern of behavioural functions mediated by imprinted genes emerging from the limited data, and also whether any tangible predictions can be made with regards to the direction of action of genes of maternal or paternal origin.

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Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis

Cited by 160 publications

References 23 publications

p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation

p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation

Siah-1L, a novel transcript variant belonging to the human Siah family of proteins, regulates β-catenin activity in a p53-dependent manner

Genomic imprinting and the social brain

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