Discovery of a novel family of putative oxidoreductases implicated in tumor developement

Although the sequence of the human genome has been known for ten years, still the molecular function of a considerable part of the human proteome (at least a quarter of all the human proteins) remains uknown. Such proteins, even if circumstantial links to human disease exist, cannot be used in building novel therapeutic hypotheses. On the other hand, if there are no hypotheses regarding the molecular function of a gene and protein, it seldom becomes to subject of detailed investigations.

In our work, we analysed proteins of unknown molecular functions, named P-DUDES by us. Many publications linked these proteins to serious human disorders (lung and gastrointestinal cancer, lymphoma, nervous system developemental disorders, and others).
Using bioinformatics methods of protein structure prediction by detecting very distant sequence similarities, we have shown that P-DUDES proteins contain domains that adopt the structuire similar to oxidoreductases ot the thioredoxin superfamily. Further analyses led us to the hypothesis that the domain functions as peroxiredoxin, an enzyme that functions in oxidative stress defense and cellular signalling.
Then, analysis of gene expression data available in databases, we have shown a link between P-DUDES gene expression and the developement of tumor of the glia tissue in the brain: the glioblastoma.
Furter, we have discovered an intriguing phylogenetic profile of the P-DUDES genes that are found only in vertebrates and a number of distant bacterial groups, mostly aquatic.
Our discovery may make the P-DUDES proteins promising novel drug targets in the future.

Date of publication
2 March 2011