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A widespread peroxiredoxin-like domain present in tumor suppression- and progression-implicated proteins.

Pawłowski, Krzysztof and Muszewska, Anna and Lenart, Anna and Szczepińska, Teresa and Godzik, Adam and Grynberg, Marcin (2010) A widespread peroxiredoxin-like domain present in tumor suppression- and progression-implicated proteins. BMC genomics, 11 . p. 590. ISSN 1471-2164



Background Peroxide turnover and signalling are involved in many biological phenomena relevant to human diseases. Yet, all the players and mechanisms involved in peroxide perception are not known. Elucidating very remote evolutionary relationships between proteins is an approach that allows the discovery of novel protein functions. Here, we start with three human proteins, SRPX, SRPX2 and CCDC80, involved in tumor suppression and progression, which possess a conserved region of similarity. Structure and function prediction allowed the definition of P-DUDES, a phylogenetically widespread, possibly ancient protein structural domain, common to vertebrates and many bacterial species. Results We show, using bioinformatics approaches, that the P-DUDES domain, surprisingly, adopts the thioredoxin-like (Thx-like) fold. A tentative, more detailed prediction of function is made, namely, that of a 2-Cys peroxiredoxin. Incidentally, consistent overexpression of all three human P-DUDES genes in two public glioblastoma microarray gene expression datasets was discovered. This finding is discussed in the context of the tumor suppressor role that has been ascribed to P-DUDES proteins in several studies. Majority of non-redundant P-DUDES proteins are found in marine metagenome, and among the bacterial species possessing this domain a trend for a higher proportion of aquatic species is observed. Conclusions The new protein structural domain, now with a broad enzymatic function predicted, may become a drug target once its detailed molecular mechanism of action is understood in detail.

Item Type:Article
Subjects:Q Science > Q Science (General)
Divisions:Department of Genetics
ID Code:135
Deposited By: Marcin Grynberg
Deposited On:05 May 2011 20:34
Last Modified:28 Mar 2012 20:36

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