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Open Access Highly Accessed Research article

Identification of novel mitosis regulators through data mining with human centromere/kinetochore proteins as group queries

Aaron R Tipton1, Kexi Wang1, Peter Oladimeji1, Shermeen Sufi1, Zhidong Gu12 and Song-Tao Liu1*

Author affiliations

1 Department of Biological Sciences, University of Toledo, Toledo, OH, 43606, USA

2 Ruijin Hospital, Shanghai, 200025, China

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Citation and License

BMC Cell Biology 2012, 13:15  doi:10.1186/1471-2121-13-15

Published: 19 June 2012

Abstract

Background

Proteins functioning in the same biological pathway tend to be transcriptionally co-regulated or form protein-protein interactions (PPI). Multiple spatially and temporally regulated events are coordinated during mitosis to achieve faithful chromosome segregation. The molecular players participating in mitosis regulation are still being unravelled experimentally or using in silico methods.

Results

An extensive literature review has led to a compilation of 196 human centromere/kinetochore proteins, all with experimental evidence supporting the subcellular localization. Sixty-four were designated as “core” centromere/kinetochore components based on peak expression and/or well-characterized functions during mitosis. By interrogating and integrating online resources, we have mined for genes/proteins that display transcriptional co-expression or PPI with the core centromere/kinetochore components. Top-ranked hubs in either co-expression or PPI network are not only enriched with known mitosis regulators, but also contain candidates whose mitotic functions are not yet established. Experimental validation found that KIAA1377 is a novel centrosomal protein that also associates with microtubules and midbody; while TRIP13 is a novel kinetochore protein and directly interacts with mitotic checkpoint silencing protein p31comet.

Conclusions

Transcriptional co-expression and PPI network analyses with known human centromere/kinetochore proteins as a query group help identify novel potential mitosis regulators.

Keywords:
Centromere; Kinetochore; Centrosome; Data mining; Protein-protein interaction; Co-expression