Cliques in mitotic spindle network bring kinetochore-associated complexes to form dependence pathway.
The mitotic spindle is an essential molecular machine for chromosome segregation during mitosis. Achieving a better understanding of its organization at the topological level remains a daunting task. To determine the functional connections among 137 mitotic spindle proteins, a protein-protein interaction network among queries was constructed. Many hub proteins, which connect more than one query and serve as highly plausible candidates for expanding the mitotic spindle proteome, are ranked by conventional degree centrality and a new subnetwork specificity score. Evaluation of the ranking results by literature reviews and empirical verification of SEPT6, a novel top-ranked hub, suggests that the subnetwork specificity score could enrich for putative spindle-related proteins. Topological analysis of this expanded network shows the presence of 30 3-cliques and six 4-cliques (fully connected subgraphs) that, respectively, reside in eight kinetochore-associated complexes, of which seven are evolution conserved. Notably, these complexes strikingly form dependence pathways for the assembly of the kinetochore complex. These analyses indicate the feasibility of using network topology, i.e. cliques, to uncover novel pathways to accelerate our understanding of potential biological processes.
Chen
Tzu-Chi
TC
Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei 112, Taiwan.
Lee
Sheng-An
SA
Chan
Chen-Hsiung
CH
Juang
Yue-Li
YL
Hong
Yi-Ren
YR
Huang
Yei-Hsuan
YH
Lai
Jin-Mei
JM
Kao
Cheng-Yan
CY
Huang
Chi-Ying F
CY
D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D040901:Proteomics / Q000379:methods*; D008941:Spindle Apparatus / Q000378:metabolism*
D009687:Nuclear Proteins