Identification of the substrates and interaction proteins of aurora kinases from a protein-protein interaction model

Document Type

Article

Abstract

The increasing use of high-throughput and large-scale bioinformatics-based studies has generated a massive amount of data stored in a number of different databases. The major need now is to explore this disparate data to find biologically relevant interactions and pathways. Thus, in the post-genomic era, there is clearly a need for the development of algorithms that can accurately predict novel protein-protein interaction networks in silico. The evolutionarily conserved Aurora family kinases have been chosen as a model for the development of a method to identify novel biological networks by a comparison of human and various model organisms. Our search methodology was designed to predict and prioritize molecular targets for Aurora family kinases, so that only the most promising are subjected to empirical testing. Four potential Aurora substrates and/or interacting proteins, TACC3, survivin, Hec1, and hsNuf2, were identified and empirically validated. Together, these results justify the timely implementation of in silico biology in routine wet-lab studies and have also allowed the application of a new approach to the elucidation of protein function in the post-genomic era.

Medical Subject Headings

Algorithms; Amino Acid Sequence; Animals; Aurora Kinases; Cell Cycle Proteins; Cell Line; Computational Biology (methods); Cytoskeletal Proteins; Evolution, Molecular; Fungal Proteins (metabolism); Humans; Inhibitor of Apoptosis Proteins; Microtubule-Associated Proteins (metabolism); Molecular Sequence Data; Neoplasm Proteins; Nuclear Proteins (metabolism); Protein Serine-Threonine Kinases (metabolism); Sequence Alignment; Survivin; Two-Hybrid System Techniques

Publication Date

1-1-2004

Publication Title

Molecular & cellular proteomics : MCP

ISSN

1535-9476

Volume

3

Issue

1

First Page

93

Last Page

104

PubMed ID

14602875

Digital Object Identifier (DOI)

10.1074/mcp.M300072-MCP200

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