Biology of Aurora A kinase: implications in cancer manifestation and therapy.
The Aurora A kinase belongs to serine/threonine group of kinases, well known for its role in cell cycle, especially in the regulation of mitosis. Numerous substrates of Aurora A kinase have been identified, which are predominantly related to cell cycle progression while some of them are transcription factors. Aurora A-mediated phosphorylation can either directly or indirectly regulate the function of its substrates. There are overwhelming evidences which report overexpression and gene amplification of Aurora A in several human cancers, and suggest that Aurora A could be a bona fide oncogene involved in tumorigenesis. Hence, Aurora A plays wide-ranging roles in both mitosis and its deregulation manifests in cancer progression. These observations have favored the choice of Aurora kinases as a target for cancer therapy. Recently, numerous small molecules have been discovered against Aurora kinases and many have entered clinical trials. Most of these small-molecule modulators designed are specific against either Aurora A or Aurora B, but some are dual inhibitors targeting the ATP-binding site which is highly conserved among the three human homologues of Aurora kinase. In this review, we discuss the physiological functions of Aurora A, interactions between Aurora A kinase and its cellular substrates, tumorigenesis mediated by Aurora A kinase upon overexpression, and small-molecule modulators of Aurora kinase as targets for cancer therapy.
Karthigeyan
Dhanasekaran
D
Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, India.
Prasad
Sallekoppal B Benaka
SB
Shandilya
Jayasha
J
Agrawal
Shipra
S
Kundu
Tapas K
TK
D000818:Animals; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D016147:Genes, Tumor Suppressor; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D011110:Polymorphism, Genetic; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology
D047428:Protein Kinase Inhibitors; D064096:Aurora Kinase A