Abstract
BackgroundProteins 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.ResultsAn 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.ConclusionsTranscriptional co-expression and PPI network analyses with known human centromere/kinetochore proteins as a query group help identify novel potential mitosis regulators.
Highlights
Proteins functioning in the same biological pathway tend to be transcriptionally co-regulated or form protein-protein interactions (PPI)
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
Experimental validation found that KIAA1377 is a novel centrosomal protein that associates with microtubules and midbody; while TRIP13 is a novel kinetochore protein and directly interacts with mitotic checkpoint silencing protein p31comet
Summary
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. The temporal and spatial changes in mitotic cells are tightly regulated to ensure high fidelity of genomic transmission during cell division. Mitosis is initiated by accumulation of active kinase complexes formed between mitotic cyclins (cyclin A and B in human) and master mitosis regulator CDC2 (or CDK1) at the G2/M transition [1]. Chromosome condensation appears during prophase, concurring with reorganization of microtubule cytoskeleton into mitotic spindles and separation of duplicated centrosomes to opposite sides of the nucleus.
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