Biology of Aurora A Kinase: Implications in Cancer Manifestation and Therapy

被引：72

作者：

Karthigeyan, Dhanasekaran ^{[1
]}

Prasad, Sallekoppal B. Benaka ^{[1
]}

Shandilya, Jayasha ^{[1
]}

Agrawal, Shipra ^{[2
]}

Kundu, Tapas K. ^{[1
]}

机构：

[1] Jawaharlal Nehru Ctr Adv Sci Res, Transcript & Dis Lab, Mol Biol & Genet Unit, Bangalore 560064, Karnataka, India

[2] Inst Bioinformat & Appl Biotechnol, Bangalore, Karnataka, India

来源：

MEDICINAL RESEARCH REVIEWS | 2011年 / 31卷 / 05期

关键词：

phosphorylation; centrosome dynamics; checkpoint; tumorigenesis; kinase inhibitors; SMALL-MOLECULE INHIBITOR; I DOSE-ESCALATION; A KINASE; CELL-CYCLE; MITOTIC SPINDLE; CRYSTAL-STRUCTURE; CENTROSOME AMPLIFICATION; STRUCTURAL BASIS; PROTEIN-KINASES; GENE-EXPRESSION;

D O I：

10.1002/med.20203

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2010 Wiley Periodicals, Inc. Med Res Rev, 31, No. 5, 757-793, 2011

引用

页码：757 / 793

页数：37

共 132 条

[11] Phase I dose escalation study of the Aurora kinase inhibitor PHA-739358 administered as a 24 hours infusion in a 14-day cycle in patients with advanced/metastatic solid tumor [J].

Burris, H. A. ;

Hudes, G. ;

Jones, S. ;

Cheng, J. ;

Spigel, D. ;

Mariani, M. ;

Macdonald, H. ;

Rocchetti, M. ;

Laffranchi, B. ;

Cohen, R. B. .

EJC SUPPLEMENTS, 2006, 4 (12) :107-107

[12] Subcellular localization of the spindle proteins Aurora A, Mad2, and BUBR1 assessed by immunohistochemistry [J].

Burum-Auensen, Espen ;

De Angelis, Paula M. ;

Schjolberg, Aasa R. ;

Kravik, Katherine L. ;

Aure, Marit ;

Clausen, Ole Petter F. .

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2007, 55 (05) :477-486

[13] The cellular geography of aurora kinases [J].

Carmena, M ;

Earnshaw, WC .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (11) :842-854

[14] PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer [J].

Carpinelli, Patrizia ;

Ceruti, Roberta ;

Giorgini, Maria Laura ;

Cappella, Paolo ;

Gianellini, Laura ;

Croci, Valter ;

Degrassi, Anna ;

Texido, Gernma ;

Rocchetti, Maurizio ;

Vianello, Paola ;

Rusconi, Luisa ;

Storici, Paola ;

Zugnoni, Paola ;

Arrigoni, Claudio ;

Soncini, Chiara ;

Alli, Cristina ;

Patton, Veronica ;

Marsiglio, Aurelio ;

Ballinari, Dario ;

Pesenti, Enrico ;

Fancelli, Daniele ;

Moll, Jurgen .

MOLECULAR CANCER THERAPEUTICS, 2007, 6 (12) :3158-3168

[15] Aurora kinases: New targets for cancer therapy [J].

Carvajal, Richard D. ;

Tse, Archie ;

Schwartz, Gary K. .

CLINICAL CANCER RESEARCH, 2006, 12 (23) :6869-6875

[16]

CHAN CSM, 1993, GENETICS, V135, P677

[17]

Chaturvedi P, 2002, CANCER RES, V62, P1797

[18] Phospho-regulation of kinetochore-microtubule attachments by the aurora kinase Ipl1p [J].

Cheeseman, LM ;

Anderson, S ;

Jwa, M ;

Green, EM ;

Kang, JS ;

Yates, JR ;

Chan, CSM ;

Drubin, DG ;

Barnes, G .

CELL, 2002, 111 (02) :163-172

[19] Structural basis for potent inhibition of the Aurora kinases and a T3151 multi-drug resistant mutant form of Abl kinase by VX-680 [J].

Cheetham, G. M. T. ;

Charlton, P. A. ;

Golec, J. M. C. ;

Pollard, J. R. .

CANCER LETTERS, 2007, 251 (02) :323-329

[20] Crystal structure of aurora-2, an oncogenic serine/threonine kinase [J].

Cheetham, GMT ;

Knegtel, RMA ;

Coll, JT ;

Renwick, SB ;

Swenson, L ;

Weber, P ;

Lippke, JA ;

Austen, DA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (45) :42419-42422

← 1 2 3 4 5 6 7 8 9 10 →