<i>p53</i>mRNA and p53 Protein Structures Have Evolved Independently to Interact with MDM2

Karakostis, Konstantinos; Ponnuswamy, Anand; Fusee, Leila; Bailly, Xavier; Laguerre, Laurent; Worall, Erin; Vojtesek, Borek; Nylander, Karin; Fåhræus, Robin

doi:10.1093/molbev/msw012

Cited by 20 publications

(35 citation statements)

References 56 publications

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“…There have been several attempts to solve the evolutionary history of the p53/p63/p73 protein family [ 6 , 13 – 15 , 20 ], but so far no phylogenetic tree, including both vertebrate and invertebrate species, has been published that agrees with the evolution of species. The phylogeny of MDM has been sparsely investigated, and the best published tree comprises only five vertebrates and three invertebrates species [ 23 ]. Due to less structural constraints, intrinsically disordered regions, like the p53/p63/p73 TAD, are allowed to substitute at a faster rate compared to structured regions [ 24 , 25 ].…”

Section: Resultsmentioning

confidence: 99%

Evolution of the p53-MDM2 pathway

et al. 2017

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BackgroundThe p53 signalling pathway, which controls cell fate, has been extensively studied due to its prominent role in tumor development. The pathway includes the tumor supressor protein p53, its vertebrate paralogs p63 and p73, and their negative regulators MDM2 and MDM4. The p53/p63/p73-MDM system is ancient and can be traced in all extant animal phyla. Despite this, correct phylogenetic trees including both vertebrate and invertebrate species of the p53/p63/p73 and MDM families have not been published.ResultsHere, we have examined the evolution of the p53/p63/p73 protein family with particular focus on the p53/p63/p73 transactivation domain (TAD) and its co-evolution with the p53/p63/p73-binding domain (p53/p63/p73BD) of MDM2. We found that the TAD and p53/p63/p73BD share a strong evolutionary connection. If one of the domains of the protein is lost in a phylum, then it seems very likely to be followed by loss of function by the other domain as well, and due to the loss of function it is likely to eventually disappear. By focusing our phylogenetic analysis to p53/p63/p73 and MDM proteins from phyla that retain the interaction domains TAD and p53/p63/p73BD, we built phylogenetic trees of p53/p63/p73 and MDM based on both vertebrate and invertebrate species. The trees follow species evolution and contain a total number of 183 and 98 species for p53/p63/p73 and MDM, respectively. We also demonstrate that the p53/p63/p73 and MDM families result from whole genome duplications.ConclusionsThe signaling pathway of the TAD and p53/p63/p73BD in p53/p63/p73 and MDM, respectively, dates back to early metazoan time and has since then tightly co-evolved, or disappeared in distinct lineages.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-017-1023-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Evolution of the p53-MDM2 pathway

et al. 2017

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“…The authors have suggested that preservation of not only the sequence but also the tertiary structure of this hairpin is crucial to maintain its function [37]. So far, there is no data concerning binding of Mdm2 to mouse p53 mRNA despite extended studies of Mdm2-p53 interactions using various cell cultures, invertebrates (C. intestinalis) [39] and mouse models [40]. Since our analyses reveled two potential different foldings of the C40 -C80 region of RNA-122 and RNA-247 we could envisage that Mdm2-mouse p53 mRNA interaction might be controlled by structural rearrangement of this region.…”

Section: Conservation Of Structural Elements Found In the 5′terminal mentioning

confidence: 99%

Length and secondary structure of the 5′ non-coding regions of mouse p53 mRNA transcripts - mouse as a model organism for p53 gene expression studies

2018

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Transcription initiation sites of Trp53 gene in mice were determined using the 5′RACE method. Based on sequence alignment of the 5′-terminal regions of p53 mRNA in mammals, the site for the most abundant transcript turned out to be essentially identical with that determined for human TP53 gene and slightly differed for the longest transcripts, in mice and humans. Secondary structures of the 5′-terminal regions of the shorter, most abundant and the longest mouse transcripts were determined in vitro and the shorter transcript was also mapped in transfected mouse cells. For the first time, secondary structure models of the 5′ terminus of two mouse p53 mRNAs were proposed. Comparing these models with the conservativeness of the nucleotide sequence of the 5′-terminal region of mRNA in mouse and other mammals, the possible function of the selected structural domains of this region was discussed. To elucidate the translation mechanisms, the two studied mRNAs were translated in the presence of an increasing concentration of the cap analog. For the longest transcript, the data suggested that IRES element(s) was/were involved in translation initiation. Additionally, changes in p53 synthesis under genotoxic and endoplasmic reticulum stress conditions in mouse cells were analyzed.

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“…The interaction between the box-I p53 mRNA and MDM2 is also present in the pre-vertebrate Ciona instestinalis (109). The pre-vertebrate p53 RNA structure is regulated by temperature and the optimal binding temperature for the p53 mRNA–MDM2 protein interaction for C. intestinalis was measured at 18 and 30°C for the mammalian (107–109).…”

Section: Introductionmentioning

confidence: 99%

The p53 mRNA: an integral part of the cellular stress response

Hároníková

Olivares‐Illana

Wang

et al. 2019

Nucleic Acids Research

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A large number of signalling pathways converge on p53 to induce different cellular stress responses that aim to promote cell cycle arrest and repair or, if the damage is too severe, to induce irreversible senescence or apoptosis. The differentiation of p53 activity towards specific cellular outcomes is tightly regulated via a hierarchical order of post-translational modifications and regulated protein-protein interactions. The mechanisms governing these processes provide a model for how cells optimize the genetic information for maximal diversity. The p53 mRNA also plays a role in this process and this review aims to illustrate how protein and RNA interactions throughout the p53 mRNA in response to different signalling pathways control RNA stability, translation efficiency or alternative initiation of translation. We also describe how a p53 mRNA platform shows riboswitch-like features and controls the rate of p53 synthesis, protein stability and modifications of the nascent p53 protein. A single cancer-derived synonymous mutation disrupts the folding of this platform and prevents p53 activation following DNA damage. The role of the p53 mRNA as a target for signalling pathways illustrates how mRNA sequences have co-evolved with the function of the encoded protein and sheds new light on the information hidden within mRNAs.

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p53mRNA and p53 Protein Structures Have Evolved Independently to Interact with MDM2

Cited by 20 publications

References 56 publications

Evolution of the p53-MDM2 pathway

Evolution of the p53-MDM2 pathway

Length and secondary structure of the 5′ non-coding regions of mouse p53 mRNA transcripts - mouse as a model organism for p53 gene expression studies

The p53 mRNA: an integral part of the cellular stress response

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