Identification of novel mitosis regulators through data mining with human centromere/kinetochore proteins as group queries.
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 p31(comet).


CONCLUSIONS
Transcriptional co-expression and PPI network analyses with known human centromere/kinetochore proteins as a query group help identify novel potential mitosis regulators.
Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
Aaron R
AR
Tipton
Kexi
K
Wang
Peter
P
Oladimeji
Shermeen
S
Sufi
Zhidong
Z
Gu
Song-Tao
ST
Liu
D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D057225:Data Mining; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints; D008870:Microtubules / Q000378:metabolism; D050258:Mitosis Modulators / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D025941:Protein Interaction Mapping; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; C575110:CEP126 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D047908:Intracellular Signaling Peptides and Proteins; C470309:MAD2L1BP protein, human; D050258:Mitosis Modulators; D009687:Nuclear Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; C575259:TRIP13 protein, human