Phosphoproteomic Analysis of Aurora Kinase Inhibition in Monopolar Cytokinesis.
Cytokinesis is the last step of the cell cycle that requires coordinated activities of the microtubule cytoskeleton, actin cytoskeleton, and membrane compartments. Aurora B kinase is one of the master regulatory kinases that orchestrate multiple events during cytokinesis. To reveal targets of the Aurora B kinase, we combined quantitative mass spectrometry with chemical genetics. Using the quantitative proteomic approach, SILAC (stable isotope labeling with amino acids in cell culture), we analyzed the phosphoproteome of monopolar cytokinesis upon VX680- or AZD1152-mediated aurora kinase inhibition. In total, our analysis quantified over 20 000 phosphopeptides in response to the Aurora-B kinase inhibition; 246 unique phosphopeptides were significantly down-regulated and 74 were up-regulated. Our data provide a broad analysis of downstream effectors of Aurora kinase and offer insights into how Aurora kinase regulates cytokinesis.
Department of Molecular Biology and Genetics, Koç University , Fen Fakultesi, Sariyer, Istanbul 34450, Turkey.
Ayse Nur
AN
Polat
Department of Molecular Biology and Genetics, Koç University , Fen Fakultesi, Sariyer, Istanbul 34450, Turkey.
Özge
Ö
Karayel
Research Group Bioinformatics (NG 4), Robert Koch-Institute , Postfach 65 02 61, D-13302 Berlin, Germany.|Department of Bioanalytics, Institute of Biotechnology, Technische Universität Berlin , Gustav-Meyer-Allee 25, 13355 Berlin, Germany.
Sven H
SH
Giese
Department of Molecular Biology and Genetics, Koç University , Fen Fakultesi, Sariyer, Istanbul 34450, Turkey.
Büşra
B
Harmanda
Department of Molecular Biology and Genetics, Koç University , Fen Fakultesi, Sariyer, Istanbul 34450, Turkey.
Erdem
E
Sanal
Department of Genetics, Stanford University, School of Medicine , 291 Campus Drive, Li Ka Shing Building, Stanford, California 94305, United States.
Chi-Kuo
CK
Hu
Research Group Bioinformatics (NG 4), Robert Koch-Institute , Postfach 65 02 61, D-13302 Berlin, Germany.
Bernhard Y
BY
Renard
Department of Molecular Biology and Genetics, Koç University , Fen Fakultesi, Sariyer, Istanbul 34450, Turkey.
Nurhan
N
Özlü
D064107:Aurora Kinase B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D048749:Cytokinesis / Q000187:drug effects / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D010750:Phosphoproteins / Q000032:analysis* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020543:Proteome / Q000032:analysis* / Q000187:drug effects* / Q000378:metabolism; D040901:Proteomics; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines
D064107:Aurora Kinase B; D010750:Phosphoproteins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D020543:Proteome; C484810:tozasertib; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines