Programmed cell death of primordial germ cells in<i>Drosophila</i>is regulated by p53 and the Outsiders monocarboxylate transporter

Yamada, Yukiko; Davis, Keri D.; Coffman, Clark R.

doi:10.1242/dev.010389

Cited by 53 publications

(59 citation statements)

References 82 publications

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“…GO term analysis of the in vitro Dmp53 interactome revealed enrichment of genes involved in gametogenesis. Because p53 mutant flies accumulate an aberrant number of primordial germ cells ectopic to the gonads (36), and p53 and p63 are involved in genoprotective apoptotic responses during mammalian gametogenesis (9,37,38), novel interactors may help dissect this functional role of the p53 family. Another notable feature of the in vitro Dmp53 interactome is the high representation of cytoplasmic and mitochondrial proteins.…”

Section: Discussionmentioning

confidence: 99%

A genome-scale protein interaction profile of Drosophila p53 uncovers additional nodes of the human p53 network

Lunardi

Minin

Provero

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The genome of the fruitfly Drosophila melanogaster contains a single p53-like protein, phylogenetically related to the ancestor of the mammalian p53 family of tumor suppressors. We reasoned that a comprehensive map of the protein interaction profile of Drosophila p53 (Dmp53) might help identify conserved interactions of the entire p53 family in man. Using a genome-scale in vitro expression cloning approach, we identified 91 previously unreported Dmp53 interactors, considerably expanding the current Drosophila p53 interactome. Looking for evolutionary conservation of these interactions, we tested 41 mammalian orthologs and found that 37 bound to one or more p53-family members when overexpressed in human cells. An RNAi-based functional assay for modulation of the p53 pathway returned five positive hits, validating the biological relevance of these interactions. One p53 interactor is GTPBP4, a nucleolar protein involved in 60S ribosome biogenesis. We demonstrate that GTPBP4 knockdown induces p53 accumulation and activation in the absence of nucleolar disruption. In breast tumors with wild-type p53, increased expression of GTPBP4 correlates with reduced patient survival, emphasizing a potential relevance of this regulatory axis in cancer.in vitro expression cloning | p73 | p63 | NOG1

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Section: Discussionmentioning

confidence: 99%

A genome-scale protein interaction profile of Drosophila p53 uncovers additional nodes of the human p53 network

Lunardi

Minin

Provero

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Flies lacking Dmp53 (the Drosophila p53 homolog) are viable, and still undergo cell cycle arrest and apoptosis following DNA damage, but display abnormal germ cell death, similarly to C. elegans (Yamada et al, 2008). Dmp53 has also been implicated in ageing.…”

Section: P53mentioning

confidence: 99%

Autophagy and ageing: Insights from invertebrate model organisms

Lionaki

Markaki

Tavernarakis

2013

Ageing Research Reviews

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a b s t r a c tAgeing in diverse species ranging from yeast to humans is associated with the gradual, lifelong accumulation of molecular and cellular damage. Autophagy, a conserved lysosomal, self-destructive process involved in protein and organelle degradation, plays an essential role in both cellular and whole-animal homeostasis. Accumulating evidence now indicates that autophagic degradation declines with age and this gradual reduction of autophagy might have a causative role in the functional deterioration of biological systems during ageing. Indeed, loss of autophagy gene function significantly influences longevity. Moreover, genetic or pharmacological manipulations that extend lifespan in model organisms often activate autophagy. Interestingly, conserved signalling pathways and environmental factors that regulate ageing, such as the insulin/IGF-1 signalling pathway and oxidative stress response pathways converge on autophagy. In this article, we survey recent findings in invertebrates that contribute to advance our understanding of the molecular links between autophagy and the regulation of ageing. In addition, we consider related mechanisms in other organisms and discuss their similarities and idiosyncratic features in a comparative manner.

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“…Of these, only a subset enters into the embryonic gonad, and the rest of the pole cells are eliminated by nonapoptotic cell death (49,50). Furthermore, pole cells are competent to undergo apoptosis, and a reduction of maternal Nanos activity, which is essential for the establishment of germ-line fate, effectively triggers programmed cell death (51,52).…”

Section: Role Of Notch Egfr and Sev Signaling Pathways In The Male mentioning

confidence: 99%

Notch and Egfr signaling act antagonistically to regulate germ-line stem cell niche formation in Drosophila male embryonic gonads

Kitadate

Kobayashi²

2010

Proc. Natl. Acad. Sci. U.S.A.

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Germ-line stem cells (GSCs) are maintained by the somatic microenvironment, or GSC niche, which ensures that GSCs can both self-renew and produce functional gametes. However, it remains unclear how the proper niche size and location are regulated within the developing gonads. In the Drosophila testis, the hub cells that form the GSC niche are derived from a subset of somatic gonadal precursors (SGPs) in the anterior portion of the embryonic gonad. Here we show that Notch signaling induces hub differentiation. Notch is activated in almost all SGPs in the male embryonic gonad, but Epidermal growth factor receptor (Egfr) is activated in posterior SGPs to repress hub differentiation, thereby restricting the expansion of hub differentiation in the embryonic gonad. We further show that Egfr is activated in posterior SGPs by Spitz ligand secreted from primordial germ cells (PGCs), whereas the Notch ligand Serrate is expressed in SGPs. This suggests that varying the number of PGCs alters niche size. Indeed, a decrease in the number of PGCs causes ectopic hub differentiation, which consequently increases their opportunity to recruit PGCs as GSCs. When ectopic hub differentiation is repressed, the decreased number of PGCs fails to become GSCs. Thus, we propose that SGPs sense PGC number via signals from PGCs to SGPs that modulate niche size, and that this serves as a mechanism for securing GSCs.

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Programmed cell death of primordial germ cells inDrosophilais regulated by p53 and the Outsiders monocarboxylate transporter

Cited by 53 publications

References 82 publications

A genome-scale protein interaction profile of Drosophila p53 uncovers additional nodes of the human p53 network

A genome-scale protein interaction profile of Drosophila p53 uncovers additional nodes of the human p53 network

Autophagy and ageing: Insights from invertebrate model organisms

Notch and Egfr signaling act antagonistically to regulate germ-line stem cell niche formation in Drosophila male embryonic gonads

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