Targeting Aurora-2 kinase in cancer.
Aurora-2 kinase has been shown to contribute to oncogenic transformation and is frequently overexpressed and amplified in many human tumor types. Aurora-2 belongs to a small family of mitotic serine/threonine kinases that regulate centrosome maturation, chromosome segregation, and cytokinesis. The mechanism behind the transforming activity of aurora-2 is not fully understood; however, the role of aurora-2 in regulating the centrosome cycle is likely responsible for its ability to transform cells. Aurora-2 overexpression has been correlated with centrosome amplification, which can be a driving cause of genomic instability in tumor cells. In addition, recent work has demonstrated that aurora-2 plays an active function in promoting entry into mitosis by regulating local translation of centrosomal stored mRNA, such as cyclin B1. These recent findings implicate aurora-2 as an important regulator of both genomic integrity and cell cycle progression in cancer cells and suggest that aurora-2 is an attractive target for anticancer drug development.
Warner
Steven L
SL
Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA.
Bearss
David J
DJ
Han
Haiyong
H
Von Hoff
Daniel D
DD
D000970:Antineoplastic Agents / Q000494:pharmacology; D064127:Aurora Kinases; D018385:Centrosome / Q000648:ultrastructure; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D015972:Gene Expression Regulation, Neoplastic; D008938:Mitosis; D008954:Models, Biological; D009369:Neoplasms / Q000201:enzymology*; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism
D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D012333:RNA, Messenger; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases