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

Krzysztof Pawłowski, Anna Muszewska, Anna Lenart, Teresa Szczepińska, Adam Godzik, Marcin Grynberg

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number590
JournalBMC Genomics
Volume11
Issue number1
DOIs
StatePublished - Oct 21 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

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