Data mining the p53 pathway in the Fugu genome: evidence for strong conservation of the apoptotic pathway

Bras, Morgane Le; Bensaad, Karim; Soussi, Thierry

doi:10.1038/sj.onc.1206424

Cited by 13 publications

(5 citation statements)

References 65 publications

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“…However, the regulation of p53 by Mdm2 may only exist in vertebrates, as so far researchers have failed to identify an Mdm2 homologue in either Drosophila or C. elegans. Analysis of the Fugu fish genome has revealed that although many of the p53 target genes such as PIG3 and PIDD, p53DINP1 are conserved, orthologues related to Fas, Bax, PUMA, Noxa and p53AIP were not found (Le Bras et al, 2003). This raises the interesting question as to which elements of the p53 response are conserved.…”

Section: Apoptosis: the Most Conserved Property Of P53mentioning

confidence: 94%

To die or not to die: how does p53 decide?

2004

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Section: Apoptosis: the Most Conserved Property Of P53mentioning

confidence: 94%

To die or not to die: how does p53 decide?

2004

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“…p53 has been cloned and characterised in several fish species and its importance during embryogenesis and DNA damage-induced apoptosis elicited by UV or by the anti-cancer compound camptothecin has been reported [125][126][127][128][129][130][131][132]. Moreover, data mining the p53 pathway in the Fugu genome has indicated conservation of the apoptotic pathway [133]. In this context, exposure of zebrafish embryos toirradiation was shown to induce substantial increase in p53-dependent activation of caspase-3 [98].…”

Section: Intrinsic Pathway In Fishmentioning

confidence: 97%

Fish and Apoptosis: Molecules and Pathways

Santos¹,

Vale²,

Reis³

et al. 2008

CPD

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Apoptosis is a genetically controlled and evolutionarily conserved form of active cell death, albeit with an increase in complexity with continuing development. A high conservation at the functional and molecular level has been described between the players of the apoptotic machinery in invertebrates (Caenorhabditis elegans and Drosophila) and mammals. However, fish represent an excellent and advantageous model for the study of vertebrate development and disease, bridging the gap between the C. elegans/Drosophila and mouse/human models. Moreover, contrary to C. elegans and Drosophila, fish can be used for studying the development and function of vertebrate-specific organs and have a fully developed immune system similar to that of mammals. Last but not less important, both the environment and human health will obviously gain by using the knowledge generated through the use of fish models, for developing better prophylactic and therapeutic measures with impact on the aquaculture industry. In the present article, structural and functional data on the most important apoptosis related molecules, namely death-receptor, Bcl-2 and caspase families, and mechanisms are reviewed. The data point to the existence in fish of apoptotic pathways equivalent to those of mammals, making fish useful animal models for studying apoptosis, which may have great applicability for the advance of the knowledge on the role of apoptotic cell death in human apoptosis-related disorders as well as in pharmaceutical design.

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“…On the macro-scale, the challenging goal of Systems Biology is to integrate the different levels of information to explore the cellular complexity [72][73][74][75][76][77][78][79][80][81][82]. The aim is to combine available experimental and computational data to characterize the network of intermolecular interactions and their regulation.…”

Section: Conclusion and Outlook: Protein Interactions And Systems Bio...mentioning

confidence: 99%

Protein–protein interactions: organization, cooperativity and mapping in a bottom-up Systems Biology approach

Keskin

Rogale

et al. 2005

Phys. Biol.

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Understanding and ultimately predicting protein associations is immensely important for functional genomics and drug design. Here, we propose that binding sites have preferred organizations. First, the hot spots cluster within densely packed 'hot regions'. Within these regions, they form networks of interactions. Thus, hot spots located within a hot region contribute cooperatively to the stability of the complex. However, the contributions of separate, independent hot regions are additive. Moreover, hot spots are often already pre-organized in the unbound (free) protein states. Describing a binding site through independent local hot regions has implications for binding site definition, design and parametrization for prediction. The compactness and cooperativity emphasize the similarity between binding and folding. This proposition is grounded in computation and experiment. It explains why summation of the interactions may over-estimate the stability of the complex. Furthermore, statistically, charge-charge coupling of the hot spots is disfavored. However, since within the highly packed regions the solvent is screened, the electrostatic contributions are strengthened. Thus, we propose a new description of protein binding sites: a site consists of (one or a few) self-contained cooperative regions. Since the residue hot spots are those conserved by evolution, proteins binding multiple partners at the same sites are expected to use all or some combination of these regions.

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Data mining the p53 pathway in the Fugu genome: evidence for strong conservation of the apoptotic pathway

Cited by 13 publications

References 65 publications

To die or not to die: how does p53 decide?

To die or not to die: how does p53 decide?

Fish and Apoptosis: Molecules and Pathways

Protein–protein interactions: organization, cooperativity and mapping in a bottom-up Systems Biology approach

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