Phylogeny and Function of the Invertebrate p53 Superfamily

Rutkowski, Rachael; Hofmann, Kay; Gartner, Anton

doi:10.1101/cshperspect.a001131

Cited by 94 publications

(93 citation statements)

References 79 publications

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“…Recent findings also implicate p53 in the regulation of lifespan. Invertebrates such as worms and flies do not develop cancer upon deletion of p53 (Rutkowski et al, 2011). Nevertheless, p53 deficiency broadly affects development, metabolism, cell death, the response to genotoxic stress and the overall fitness of the organism, which may account for the impact of p53 on life expectancy ( Fig.…”

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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Section: P53mentioning

confidence: 99%

Autophagy and ageing: Insights from invertebrate model organisms

Lionaki

Markaki

Tavernarakis

2013

Ageing Research Reviews

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“…The idea that the C. elegans germline recapitulates apoptotic mechanisms found in mammalian cells was reinforced by the identi fi cation of a p53 homolog in the worm genome, cep-1 ( C. elegans p 53-like 1 ) (Derry et al 2001 ;Schumacher et al 2001 ; for recent reviews, see Rutkowski et al 2010 ) . The identity of cep-1 remained elusive despite the C. elegans genome sequence being known for several years, based on its low level of sequence conservation, which is essentially restricted to its DNA-binding domain.…”

Section: Pathways Leading To Dna Damage-induced Apoptosismentioning

confidence: 99%

“…The identity of cep-1 remained elusive despite the C. elegans genome sequence being known for several years, based on its low level of sequence conservation, which is essentially restricted to its DNA-binding domain. In mammals, the p53 family of transcription factors includes p63 and p73 and phylogenetic analysis that included many invertebrate species indicated that the radiation into those three groups occurred during vertebrate evolution (Rutkowski et al 2010 ) . However, it was recently shown that placozoans, which are very simple animals, and ticks have Mdm2-like proteins and p53 family members much more related to mammalian p53 (Lane et al 2010a, b ) .…”

Section: Pathways Leading To Dna Damage-induced Apoptosismentioning

confidence: 99%

“…The identi fi cation of CEP-1 and the tremendous interest in the mammalian p53 family prompted searches for CEP-1 regulatory mechanisms. Below, some of these mechanisms are described but other reviews are more comprehensive and include all components identi fi ed (Gartner et al 2008 ;Rutkowski et al 2010 ) . Studying CEP-1 regulation in an intact developmental system allows the addressing not only of how CEP-1 function is activated or inactivated, but also how apoptosis induction might be restricted to a certain germ cell compartment.…”

Section: Pathways Leading To Dna Damage-induced Apoptosismentioning

confidence: 99%

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Germ Cell Apoptosis and DNA Damage Responses

Bailly

Gartner

2012

Advances in Experimental Medicine and Biology

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In the past 12 years, since the fi rst description of C. elegans germ cell apoptosis, this area of research rapidly expanded. It became evident that multiple genetic pathways lead to the apoptotic demise of germ cells. We are only beginning to understand how these pathways that all require the CED-9/Bcl-2, Apaf-1/CED-4 and CED-3 caspase core apoptosis components are regulated. Physiological apoptosis, which likely accounts for the elimination of more than 50% of all germ cells, even in unperturbed conditions, is likely to be required to maintain tissue homeostasis. The best-studied pathways lead to DNA damage-induced germ cell apoptosis in response to a variety of genotoxic stimuli. This apoptosis appears to be regulated similar to DNA damage-induced apoptosis in the mouse germ line and converges on p53 family transcription factors. DNA damage response pathways not only lead to apoptosis induction, but also directly affect DNA repair, and a transient cell cycle arrest of mitotic germ cells. Finally, distinct pathways activate germ cell apoptosis in response to defects in meiotic recombination and meiotic chromosome pairing.

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“…This result is consistent with findings that these regulators evolved first in Choanozoans from the Opisthokonta group (Rutkowski et al. 2010). p21 and pRb are also absent in Giardia .…”

Section: Resultsmentioning

confidence: 99%

Constitutive aneuploidy and genomic instability in the single‐celled eukaryote Giardia intestinalis

et al. 2016

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Giardia intestinalis is an important single‐celled human pathogen. Interestingly, this organism has two equal‐sized transcriptionally active nuclei, each considered diploid. By evaluating condensed chromosome numbers and visualizing homologous chromosomes by fluorescent in situ hybridization, we determined that the Giardia cells are constitutively aneuploid. We observed karyotype inter‐and intra‐population heterogeneity in eight cell lines from two clinical isolates, suggesting constant karyotype evolution during in vitro cultivation. High levels of chromosomal instability and frequent mitotic missegregations observed in four cell lines correlated with a proliferative disadvantage and growth retardation. Other cell lines, although derived from the same clinical isolate, revealed a stable yet aneuploid karyotype. We suggest that both chromatid missegregations and structural rearrangements contribute to shaping the Giardia genome, leading to whole‐chromosome aneuploidy, unequal gene distribution, and a genomic divergence of the two nuclei within one cell. Aneuploidy in Giardia is further propagated without p53‐mediated cell cycle arrest and might have been a key mechanism in generating the genetic diversity of this human pathogen.

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Phylogeny and Function of the Invertebrate p53 Superfamily

Cited by 94 publications

References 79 publications

Autophagy and ageing: Insights from invertebrate model organisms

Autophagy and ageing: Insights from invertebrate model organisms

Germ Cell Apoptosis and DNA Damage Responses

Constitutive aneuploidy and genomic instability in the single‐celled eukaryote Giardia intestinalis

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