Interspecies data mining to predict novel ING-protein interactions in human.
BACKGROUND
The INhibitor of Growth (ING) family of type II tumor suppressors (ING1-ING5) is involved in many cellular processes such as cell aging, apoptosis, DNA repair and tumorigenesis. To expand our understanding of the proteins with which the ING proteins interact, we designed a method that did not depend upon large-scale proteomics-based methods, since they may fail to highlight transient or relatively weak interactions. Here we test a cross-species (yeast, fly, and human) bioinformatics-based approach to identify potential human ING-interacting proteins with higher probability and accuracy than approaches based on screens in a single species.


RESULTS
We confirm the validity of this screen and show that ING1 interacts specifically with three of the three proteins tested; p38MAPK, MEKK4 and RAD50. These novel ING-interacting proteins further link ING proteins to cell stress and DNA damage signaling, providing previously unknown upstream links to DNA damage response pathways in which ING1 participates. The bioinformatics approach we describe can be used to create an interaction prediction list for any human proteins with yeast homolog(s).


CONCLUSIONS
None of the validated interactions were predicted by the conventional protein-protein interaction tools we tested. Validation of our approach by traditional laboratory techniques shows that we can extract value from the voluminous weak interaction data already elucidated in yeast and fly databases. We therefore propose that the weak (low signal to noise ratio) data from large-scale interaction datasets are currently underutilized.
Gordon
Paul M K
PM
Department of Biochemistry & Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. gordonp@ucalgary.ca
Soliman
Mohamed A
MA
Bose
Pinaki
P
Trinh
Quang
Q
Sensen
Christoph W
CW
Riabowol
Karl
K
D017766:Acid Anhydride Hydrolases; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D019295:Computational Biology / Q000379:methods*; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000737:chemistry; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D048768:MAP Kinase Kinase Kinase 4 / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D016415:Sequence Alignment; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D048768:MAP Kinase Kinase Kinase 4; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes
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