From midbody protein-protein interaction network construction to novel regulators in cytokinesis.
Midbody, a transient organelle-like structure, is known as central for abscission and is indispensable for termination of cytokinesis. Here, we used the midbody proteome inventories to construct the potential midbody protein-protein interaction (PPI) network. To delineate novel regulators participating in cytokinesis, the z-score, a standard statistic score, rather than hub degree was implemented to prioritize the novel hubs. Of these hubs, KIAA0133, SEPT1, KIAA1377, and CRMP-1 were localized to the midbody, whereas HTR3A and ICAM2 were associated with the cleavage furrow as examined by immunofluorescence. Knockdown of SEPT1 and KIAA1377 resulted in increasing numbers of cytokinesis defect cells, suggesting these newly identified hubs play critical roles in cytokinesis progression. Moreover, ectopic expression of CRMP-1 mutant in which Aurora-A phosphorylation sites have been replaced with Ala results in a cytokinesis defect. This subproteome network construction not only sheds light on the intimate interactions of the midbody proteomes, but also prioritizes novel hubs or protein complexes that may govern the process of cytokinesis.
Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC.
Tzu-Chi
TC
Chen
Sheng-An
SA
Lee
Tse-Ming
TM
Hong
Jin-Yuan
JY
Shih
Jin-Mei
JM
Lai
Hsin-Ying
HY
Chiou
Shuenn-Chen
SC
Yang
Chen-Hsiung
CH
Chan
Cheng-Yan
CY
Kao
Pan-Chyr
PC
Yang
Chi-Ying F
CY
Huang
D000595:Amino Acid Sequence; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D048749:Cytokinesis / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D015388:Organelles / Q000737:chemistry*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D025941:Protein Interaction Mapping / Q000379:methods; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D000098855:Collapsin Response Mediator Protein 1
D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D020543:Proteome; D011993:Recombinant Fusion Proteins; D000098855:Collapsin Response Mediator Protein 1; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases