TY - JOUR
T1 - A widespread peroxiredoxin-like domain present in tumor suppression- and progression-implicated proteins
AU - Pawłowski, Krzysztof
AU - Muszewska, Anna
AU - Lenart, Anna
AU - Szczepińska, Teresa
AU - Godzik, Adam
AU - Grynberg, Marcin
N1 - Funding Information:
We thank the anonymous reviewers for their valuable comments and suggestions. K. P., A. L. and T. S. were supported by the Polish Ministry of Science and Higher Education grant N N301 3165 33. M. G. and A. M. were supported by the Polish Ministry of Science and Higher Education grants N N303 0178 33 and N N401 3126 33. A. G. was supported by NIH grant R01 GM087218.
PY - 2010/10/21
Y1 - 2010/10/21
N2 - 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.
AB - 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.
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U2 - 10.1186/1471-2164-11-590
DO - 10.1186/1471-2164-11-590
M3 - Article
C2 - 20964819
AN - SCOPUS:77958029232
SN - 1471-2164
VL - 11
JO - BMC Genomics
JF - BMC Genomics
IS - 1
M1 - 590
ER -