The product of the von Hippel-Lindau tumor suppressor gene stabilizes microtubules by inhibiting GTPase activity.

BackgroundProkaryotic environmental adaptations occur at different levels within cells to ensure the preservation of genome integrity, proper protein folding and function as well as membrane fluidity. Although specific composition and structure of cellular components suitable for the variety of extreme conditions has already been postulated, a systematic study describing such adaptations has not yet been performed. We therefore explored whether the environmental niche of a prokaryote could be deduced from the sequence of its proteome. Finally, we aimed at finding the precise differences between proteome sequences of prokaryotes from different environments.ResultsWe analyzed the proteomes of 192 prokaryotes from different habitats. We collected detailed information about the optimal growth conditions of each microorganism. Furthermore, we selected 42 physico-chemical properties of amino acids and computed their values for each proteome. Further, on the same set of features we applied two fundamentally different machine learning methods, Support Vector Machines and Random Forests, to successfully classify between bacteria and archaea, halophiles and non-halophiles, as well as mesophiles, thermophiles and mesothermophiles. Finally, we performed feature selection by using Random Forests.ConclusionsTo our knowledge, this is the first time that three different classification cases (domain of life, halophilicity and thermophilicity) of proteome adaptation are successfully performed with the same set of 42 features. The characteristic features of a specific adaptation constitute a signature that may help understanding the mechanisms of adaptation to extreme environments.

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Cancer-associated mutations in oncogene products and tumor suppressors contributing to tumor progression manifest themselves, at least in part, by deregulating microtubule (MT)-dependent cellular processes that play important roles in many cell biological pathways including intracellular transport, cell architecture and primary cilium and mitotic spindle organization. An essential characteristic of MTs in the performance of these varied cell processes is their ability to continuously remodel, a phenomenon known as dynamic instability. It is therefore conceivable that part of the normal function of certain cancer-causing genes is to regulate MT dynamic instability. Here we report the results of a high-resolution live cell image-based RNA interference screen targeting a collection of 70 human tumor suppressor genes to uncover cancer genes affecting MT dynamic instability. Extraction and computational analysis of MT dynamics from EB3-GFP time-lapse image sequences identified the products of the tumor suppressor genes NF1 and NF2 as potent MT-stabilizing proteins. Further in-depth characterization of NF2 revealed that it binds to and stabilizes MTs through attenuation of tubulin turnover by lowering both rates of MT polymerization and depolymerization as well as by reducing the frequency of MT catastrophes. The latter function appears to be mediated, in part, by inhibition of hydrolysis of tubulin-bound GTP on the growing MT plus end.

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In this study, we propose a novel way to describe the variety of environmental adaptations of Archaea. We have clustered 57 Archaea by using a non-redundant set of proteomic features, and verified that the clusters correspond to environmental adaptations to the archaeal habitats. The first cluster consists dominantly of hyperthermophiles and hyperthermoacidophilic aerobes. The second cluster joins together halophilic and extremely halophilic Archaea, while the third cluster contains mesophilic (mostly methanogenic) Archaea together with thermoacidophiles. The non-redundant subset of proteomic features was found to consist of five features: the ratio of charged residues to uncharged, average protein size, normalized frequency of beta-sheet, normalized frequency of extended structure and number of hydrogen bond donors. We propose this clustering to be termed phyloecological clustering. This approach could give additional insights into relationships among archaeal species that may be hidden by sole phylogenetic analysis.

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<p>PDF file - 1250K, NF2 is a stabilizer of microtubules.</p>