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Gregory D Amoutzias

Publications and source records attributed to Gregory D Amoutzias.

3 recordsLinked to original sources

Reduction/oxidation-phosphorylation control of DNA binding in the bZIP dimerization network.

BACKGROUND: bZIPs are transcription factors that are found throughout the eukarya from fungi to flowering plants and mammals. They contain highly conserved basic region (BR) and leucine zipper (LZ) domains and often function as environmental sensors. Specifically, bZIPs frequently have a role in mediating the response to oxidative stress, a crucial environmental signal that needs to be transduced to the gene regulatory network. RESULTS: Based on sequence comparisons and experimental data on a number of important bZIP transcription factors, we predict which bZIPs are under redox control and which are regulated via protein phosphorylation. By integrating genomic, phylogenetic and functional data from the literature, we then propose a link between oxidative stress and the choice of interaction partners for the bZIP proteins. CONCLUSION: This integration permits the bZIP dimerization network to be interpreted in functional terms, especially in the context of the role of bZIP proteins in the response to environmental stress. This analysis demonstrates the importance of abiotic factors in shaping regulatory networks.

Amino Acid Sequence↗

Phylogenetic profiling of protein interaction networks in eukaryotic transcription factors reveals focal proteins being ancestral to hubs.

The combination of genomic, proteomic and other data, enables to reconstruct the evolution of complex cellular units thus transcending the more reductionistic view of traditional molecular phylogeny. However, most models which try to investigate the evolution of protein interaction networks so far are based on the analysis of their global statistical properties, such as their scale-free behaviour. We have investigated phylogenies of three families of ancient eukaryotic transcription factors for which fairly reliable interaction data are available. For all three families, bZIP, bHLH and NR (nuclear receptors), we find that homo-dimerising proteins were probably the ancestors and that series of single gene duplications, in combination with domain-rearrangements, were the main driving force in establishing the basic network architecture. However, the overall scaling behaviour does not always precisely confer to some theoretical models on network evolution. In conclusion, new models which reflect the biological details of molecular evolution, need to be developed.

Basic-Leucine Zipper Transcription Factors↗

Convergent evolution of gene networks by single-gene duplications in higher eukaryotes.

By combining phylogenetic, proteomic and structural information, we have elucidated the evolutionary driving forces for the gene-regulatory interaction networks of basic helix-loop-helix transcription factors. We infer that recurrent events of single-gene duplication and domain rearrangement repeatedly gave rise to distinct networks with almost identical hub-based topologies, and multiple activators and repressors. We thus provide the first empirical evidence for scale-free protein networks emerging through single-gene duplications, the dominant importance of molecular modularity in the bottom-up construction of complex biological entities, and the convergent evolution of networks.

Eukaryotic Cells↗