Mitotic requirement for aurora A kinase is bypassed in the absence of aurora B kinase.
We investigated why treatment of cells with dual aurora A and B kinase inhibitors produces phenotypes identical to inactivation of aurora B. We found that dual aurora kinase inhibitors in fact potently inhibit cellular activities of both kinases, indicating that inactivation of aurora B bypasses aurora A in mitosis. RNAi experiments further established that inactivation of aurora B indeed bypasses the requirement for aurora A and leads to polyploidy. Inactivation of aurora A activates checkpoint kinase BubR1 in an aurora B-dependent manner. Our results thus show that aurora B is responsible for mitotic arrest in the absence of aurora A.
Yang
Hui
H
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Burke
Teresa
T
Dempsey
Jack
J
Diaz
Bruce
B
Collins
Elizabeth
E
Toth
John
J
Beckmann
Richard
R
Ye
Xiang
X
D064107:Aurora Kinase B; D064127:Aurora Kinases; D001549:Benzamides / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D011123:Polyploidy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011799:Quinazolines / Q000494:pharmacology; D034622:RNA Interference; D013449:Sulfonamides / Q000494:pharmacology
C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; D001549:Benzamides; D018797:Cell Cycle Proteins; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D013449:Sulfonamides; D011494:Protein Kinases; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; C474723:hesperadin