gene section · 2016. 6. 20. · aurkb (aurora kinase b) yeung scj atlas genet cytogenet oncol...

Gene Section Review

Atlas Genet Cytogenet Oncol Haematol. 2014; 18(12) 872

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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AURKB (aurora kinase B) Sai-Ching Jim Yeung

The University of Texas M. D. Anderson Cancer Center, Department of General Internal Medicine, Ambulatory Treatment and Emergency Care, Department of Endocrine Neoplasia and Hormonal Disorders, 1515 Holcombe Boulevard, Unit 1468, Houston, Texas 77230-1402, USA (SCJY)

Published in Atlas Database: March 2014

Online updated version : http://AtlasGeneticsOncology.org/Genes/AURKBID731ch17p13.html DOI: 10.4267/2042/54365

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2014 Atlas of Genetics and Cytogenetics in Oncology and Haematology

Abstract Review on AURKB, with data on DNA/RNA, on the protein encoded and where the gene is implicated.

Identity Other names: AIK2, AIM-1, AIM1, ARK2, AurB, IPL1, PPP1R48, STK12, STK5, aurkb-sv1, aurkb-sv2

HGNC (Hugo): AURKB

Location: 17p13.1

DNA/RNA Description Aurora kinases are conserved during eukaryotic evolution. While the genomes of yeasts encode only one Aurora kinase (Ipl1 in budding yeast and Ark1 in fission yeast), higher eukaryotes express two or more members of this family. In mammals, there are three members (Aurora A, B and C).

AURKB (aurora kinase B) Yeung SCJ


Schematic diagram of protein domains of Aurora B kinase and some key facts. DN -K106R marks the location of amino acid K at position 106 (ATP binding site), which will produce a dominant negative protein when K is mutated to R. T at position 232 is the phosphorylation site involved in autocatalysis. The A-Box and D-Box are consensus sequences for targeted polyubiquitination (King et al., 1996; Pfleger and Kirschner, 2000), and the A-Box in Aurora B is important for Aurora B degradation (Nguyen et al., 2005).

Aurora A (Aurora 2, ARK1, and BTAK) is present among all vertebrates. Aurora B (Aurora 1, ARK2, and AIM1) and Aurora-C (Aurora 3 and AIK3) came into existence from gene duplication during the evolution of mammals (Brown et al., 2004).

Protein Description Size: 344 amino acids; molecular weight: 39.3 kDa. The AURKB gene has 8 exons, but there are 4 isoforms of AURKB protein due to alternative splicing. The molecular structure of Aurora B has been determined by crystallography (Sessa et al., 2005; Andersen et al., 2008; Girdler et al., 2008). When the amino acid sequences of the ATP-binding pockets of Aurora A, B and C are compared, 3 of the 26 residues lining the active site in Aurora A, Leu215, Thr217 and R220, are different from the corresponding residues in Aurora B and C (Brown et al., 2004); there is no difference in these 26 residues between Aurora B and C. The manner in which Aurora A binds to ATP (Bayliss et al., 2003) and ADP (Nowakowski et al., 2002) have been modeled. Because of the high degree of conservation of the active site between Aurora A and B, Aurora B is expected to interact with ATP and ADP in the same way as reported for Aurora A. INCENP interacts with AURKB at an α-helix domain and activates AURKB. AURKB-Sv1 lacks the INCENP interaction domain because part of exon 5 is missing and intron 5 and intron 6 may form a new domain. Therefore, the conformation of AURKB-Sv1 is expected to be different from

AURKB, and the interaction with INCENP will be affected. In contrast, the α-helix domain for interacting with INCENP is intact in AURKB-Sv2, but AURKB-Sv2 is missing major parts of the kinase domain. Thus, AURKB-Sv2 does not have kinase activity and may act as a dominant negative competitor against AURKB. Small molecule inhibitors target the ATP-binding pocket of aurora kinases. There are data available from the Protein Data Bank website (http://www.pdg.org) regarding the interaction of Aurora B with 3 inhibitors [AD6 (4-[(5-bromo-1,3-thiazol-2-yl) amino]-N-methylbenzamide): PDB ID 2vgp (Andersen et al., 2008), ZM447439: PDB ID 2vrx (Girdler et al., 2008), and hesperadin: PDB ID 2bfy (Sessa et al., 2005)].

Expression The expression of Aurora kinases varies with cell cycle phases, being at very low levels in the non-M phases (Fu et al., 2007; Gautschi et al., 2008; Mountzios et al., 2008). Although Aurora A and Aurora B are phylogenetically related, they have different biological functions and distinct temporo-spatial subcellular localization in mammals. In prophase, Aurora A is at the centrosomes while Aurora B starts to appear in the nucleus (Carmena and Earnshaw, 2003). In metaphase, Aurora A is near the spindle poles on the microtubules ends while Aurora B is on the centromeric regions of chromosomes as a chromosomal passenger protein.



AURKB has 4 alternative splicing variants: the longest one (344 aa); AURKB-Sv1 (312 aa), which loses part of exon 5 but contains a fragment of intron 5 and intron 6 instead; AURKB-Sv2 (303 aa), which lacks exon 6; and the shortest form (142 aa), which loses more than the C-terminal half of the protein (López-Saavedra and Herrera, 2010). The serines and threonines are highlighted to demonstrate the alignment. Helix domains are highlighted in magenta. The active site is highlighted in red. The nucleotide binding region is indicated by the rectangle.

The surface model of ZM447439 bound to Aurora B (amino acid 77-361) is rendered using the program PyMOL. ZM447439 (in stick molecular structure) is shown in the active site ATP-binding pocket of Aurora B (blue), and the 3 residues that differ between Aurora B and A are highlighted in cyan. INCENP-A (amino acid 798-840) in complex with Aurora B is hidden by coloring it black.



In anaphase, Aurora A is at the polar microtubules while Aurora B relocates from the centromeres to the spindle midzone (spindle equator) where the microtubules from opposite poles interdigitate (Keen and Taylor, 2004). In cytokinesis, Aurora B accumulates at the cleavage furrow before finally concentrating at the midbody.

Localisation The protein level and kinase activity of Aurora B are tightly controlled according to the phase of the cell cycle and the stages in mitosis. It expression peaks at the G2-M transition, whereas its kinase activity and subcellular localization change quickly according to the stage of mitosis. In mitosis, Aurora B, Survivin, Borealin and INCENP form the chromosomal passenger complex (Knauer et al., 2007). It is located at the chromosomes in prophase, the centromeres in prometaphase and metaphase, the central mitotic spindle in anaphase, and the cleavage furrow in cytokinesis (Adams et al., 2001). Analysis of the dynamics of Aurora B showed that the association of Aurora B with centromeres is dynamic (Murata-Hori et al., 2002) but the association with spindle microtubules during anaphase is static. Aurora B is transported to the equatorial cell cortex by astral microtubules.

Function In mitosis, the chromosomal passenger complex, composed of Aurora B, Survivin, Borealin and INCENP, controls chromosome alignment, histone modification, and cytokinesis (Knauer et al., 2007). Presence of this complex at the right place at the right time is the key to precise control of its enzymatic core, i.e., the Aurora B kinase (Vader et al., 2006). Although Aurora B Kinase is found in complexes that contain Borealin, it is not required for the mitotic phosphorylation of Borealin (Kaur et al., 2007). Thus far, there are a number of known substrates of Aurora B: the RNA methyltransferase NSUN2 (Sakita-Suto et al., 2007), Septin-1 (Qi et al., 2005), vimentin (Goto et al., 2003), histone H3 (Sugiyama et al., 2002), MgcRacGAP (Minoshima et al., 2003), INCENP (Bishop and Schumacher, 2002; Honda et al., 2003), Survivin (Wheatley et al., 2007) and TP53 (Gully et al., 2012). Aurora B activity is regulated in a variety of ways. It autophosphorylates at T232 through interaction with INCENP (Yasui et al., 2004). The phosphorylation of T232 is indispensable for its kinase activity. The temporo-spatial dynamics of Aurora B is determined by its binding to tubulin (Warner et al., 2006), regulation by other kinases and phosphatases (Sugiyama et al., 2002; Gruneberg et al., 2004), and proteasomal degradation after poly-ubiquitination (Nguyen et al., 2005; Stewart and Fang, 2005; Sumara et al., 2007). Survivin (Chen et al., 2003) and protein

serine/threonine phosphatase type 1 (PP1) or type 2A (PP2A) (Sugiyama et al., 2002) regulate Aurora B kinase activation while MKlp2 controls Aurora B localization in anaphase (Gruneberg et al., 2004). Regarding mitotic chromosome condensation, Aurora B directly phosphorylates histone H3, not only at S10 but also at S28. The level of S28 phosphorylation is rendered undetectable by PP1 just prior to entry into mitosis (Goto et al., 2002). Aurora B binds three other chromosome passenger proteins - inner centromere protein (INCENP), Survivin and Borealin - to form a complex that targets Aurora B to both centromeres and the spindle. The assembly of the outer kinetochore, which binds microtubules to control chromosome movement, is restricted to mitosis, whereas the inner kinetochore remains tethered to the centromeres throughout the cell cycle. Aurora B and PP1 coordinate and mediate cell cycle-dependent changes in kinetochore assembly by regulating the phosphorylation status of kinetochore substrates (Emanuele et al., 2008). The binding of mitotic checkpoint kinase Budding Uninhibited by Benzimidazoles1 beta (BubR1) to kinetochores is regulated by the survivin/Aurora B complex. Aurora B phosphorylates mitotic centromere-associated kinesin (MCAK) at merotelic attachments and regulates the microtubule depolymerase activity of MCAK (Knowlton et al., 2006). These functions of Aurora B are essential for proper chromosome segregation (Lens and Medema, 2003). Aurora B regulates the cleavage furrow-specific vimentin by phosphorylation and controls vimentin filament segregation in cytokinesis (Goto et al., 2003). Checkpoint kinase 1 (Chk1) is a component of the DNA damage checkpoint, and it augments spindle checkpoint signaling by activating Aurora B and BubR1 (Zachos et al., 2007). Aurora B kinase activity is also regulated by poly(ADP-ribosyl)ation; activation of Poly [ADP-ribose] polymerase 1 (PARP1) in response to DNA damage will lead to a striking inhibition of Aurora B kinase activity by poly(ADP-ribosyl)ation (Monaco et al., 2005).

Homology Intriguingly, replacing the amino acid residue G198 of Aurora A with the equivalent residue N142 of Aurora B, i.e., Aurora A (G198N), makes this single amino acid mutant behave like Aurora B (Fu et al., 2009). Aurora A (G198N) is localized in the inner centromere in metaphase and the midzone in anaphase just like Aurora B, and it can compensate for the loss of Aurora B in chromosome misalignment and premature exit from mitosis. It binds to and phosphorylates INCENP and Survivin. Therefore, the presence of glycine (G) or asparagines (N) at a single site assigns Aurora A-



like or B-like functions and properties (Fu et al., 2009).

Implicated in Lung adenocarcinoma Note (Smith et al., 2005; Vischioni et al., 2006)

Prognosis High Aurora B expression predicts short survival for lung adenocarcinoma (Vischioni et al., 2006).

Oncogenesis High Aurora B expression correlates with cell proliferation, dedifferentiation, and metastasis in lung cancer patients (Vischioni et al., 2006).

Acute myeloid leukemia Note (Ikezoe et al., 2007)

Oncogenesis In an analysis comparing 44 samples of freshly isolated AML cells with 11 bone marrow mononuclear cells from healthy volunteers and 12 peripheral blood mononuclear cells from healthy volunteers, measurement of relative mRNA expression of Aurora B shows that it is upregulated in the majority of cases (Ikezoe et al., 2007). In high-risk myelodysplastic syndrome and secondary AML, surviving and aurora B are expressed in high levels in the CD34+ cells (Yoshida et al., 2012). Aurora B overexpression may have contributed to genomic instability and progression from myelodysplastic syndrome to AML.

Prostate cancer Note (Ditchfield et al., 2003; Chieffi et al., 2006)

Oncogenesis Aurora B expression correlates with prostate cancer cell proliferation (Chieffi et al., 2006).

Anaplastic thyroid carcinomas Note (Sorrentino et al., 2005)

Oncogenesis Aurora B overexpression promotes thyroid carcinoma cell proliferation and is associated with undifferentiated thyroid cancer (Sorrentino et al., 2005).

Hepatocellular carcinoma Note (Sistayanarain et al., 2006)

Prognosis High Aurora B expression predicts short survival for hepatocellular carcinoma (Tanaka et al., 2008).

Yasen et al. (Yasen et al., 2009) studied the expression of the isoforms of Aurora B in 10 HCC cell lines and 253 samples from patients with varying degrees of HCC malignancy. AURKB was aberrantly expressed in HCC cell lines and primary HCC tumors.

Abnormal protein Expression of AURKB-Sv2 is associated with advanced stages of HCC, high levels of α-fetoprotein, tumor invasion, multiple tumor formation, and shortened disease-free survival (Yasen et al., 2009). AURKB-Sv2 may be a marker of poor prognosis.

Oncogenesis Cell cycle phase-inappropriate phosphorylation of histone H3 in the entire cell cycle may enhance proliferation of liver cancer cells (Sistayanarain et al., 2006).

Glioblastoma multiforme Note (Zeng et al., 2007)

Prognosis High Aurora B expression predicts short survival for glioblastoma multiforme (Zeng et al., 2007).

References King RW, Glotzer M, Kirschner MW. Mutagenic analysis of the destruction signal of mitotic cyclins and structural characterization of ubiquitinated intermediates. Mol Biol Cell. 1996 Sep;7(9):1343-57

Pfleger CM, Kirschner MW. The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1. Genes Dev. 2000 Mar 15;14(6):655-65

Adams RR, Carmena M, Earnshaw WC. Chromosomal passengers and the (aurora) ABCs of mitosis. Trends Cell Biol. 2001 Feb;11(2):49-54

Bishop JD, Schumacher JM. Phosphorylation of the carboxyl terminus of inner centromere protein (INCENP) by the Aurora B Kinase stimulates Aurora B kinase activity. J Biol Chem. 2002 Aug 2;277(31):27577-80

Goto H, Yasui Y, Nigg EA, Inagaki M. Aurora-B phosphorylates Histone H3 at serine28 with regard to the mitotic chromosome condensation. Genes Cells. 2002 Jan;7(1):11-7

Murata-Hori M, Tatsuka M, Wang YL. Probing the dynamics and functions of aurora B kinase in living cells during mitosis and cytokinesis. Mol Biol Cell. 2002 Apr;13(4):1099-108

Nowakowski J, Cronin CN, McRee DE, Knuth MW, Nelson CG, Pavletich NP, Rogers J, Sang BC, Scheibe DN, Swanson RV, Thompson DA. Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography. Structure. 2002 Dec;10(12):1659-67

Sugiyama K, Sugiura K, Hara T, Sugimoto K, Shima H, Honda K, Furukawa K, Yamashita S, Urano T. Aurora-B associated protein phosphatases as negative regulators of kinase activation. Oncogene. 2002 May 9;21(20):3103-11



Bayliss R, Sardon T, Vernos I, Conti E. Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. Mol Cell. 2003 Oct;12(4):851-62

Carmena M, Earnshaw WC. The cellular geography of aurora kinases. Nat Rev Mol Cell Biol. 2003 Nov;4(11):842-54

Chen J, Jin S, Tahir SK, Zhang H, Liu X, Sarthy AV, McGonigal TP, Liu Z, Rosenberg SH, Ng SC. Survivin enhances Aurora-B kinase activity and localizes Aurora-B in human cells. J Biol Chem. 2003 Jan 3;278(1):486-90

Ditchfield C, Johnson VL, Tighe A, Ellston R, Haworth C, Johnson T, Mortlock A, Keen N, Taylor SS. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol. 2003 Apr 28;161(2):267-80

Goto H, Yasui Y, Kawajiri A, Nigg EA, Terada Y, Tatsuka M, Nagata K, Inagaki M. Aurora-B regulates the cleavage furrow-specific vimentin phosphorylation in the cytokinetic process. J Biol Chem. 2003 Mar 7;278(10):8526-30

Honda R, Körner R, Nigg EA. Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. Mol Biol Cell. 2003 Aug;14(8):3325-41

Lens SM, Medema RH. The survivin/Aurora B complex: its role in coordinating tension and attachment. Cell Cycle. 2003 Nov-Dec;2(6):507-10

Minoshima Y, Kawashima T, Hirose K, Tonozuka Y, Kawajiri A, Bao YC, Deng X, Tatsuka M, Narumiya S, May WS Jr, Nosaka T, Semba K, Inoue T, Satoh T, Inagaki M, Kitamura T. Phosphorylation by aurora B converts MgcRacGAP to a RhoGAP during cytokinesis. Dev Cell. 2003 Apr;4(4):549-60

Brown JR, Koretke KK, Birkeland ML, Sanseau P, Patrick DR. Evolutionary relationships of Aurora kinases: implications for model organism studies and the development of anti-cancer drugs. BMC Evol Biol. 2004 Oct 12;4:39

Gruneberg U, Neef R, Honda R, Nigg EA, Barr FA. Relocation of Aurora B from centromeres to the central spindle at the metaphase to anaphase transition requires MKlp2. J Cell Biol. 2004 Jul 19;166(2):167-72

Keen N, Taylor S. Aurora-kinase inhibitors as anticancer agents. Nat Rev Cancer. 2004 Dec;4(12):927-36

Yasui Y, Urano T, Kawajiri A, Nagata K, Tatsuka M, Saya H, Furukawa K, Takahashi T, Izawa I, Inagaki M. Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis. J Biol Chem. 2004 Mar 26;279(13):12997-3003

Monaco L, Kolthur-Seetharam U, Loury R, Murcia JM, de Murcia G, Sassone-Corsi P. Inhibition of Aurora-B kinase activity by poly(ADP-ribosyl)ation in response to DNA damage. Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14244-8

Nguyen HG, Chinnappan D, Urano T, Ravid K. Mechanism of Aurora-B degradation and its dependency on intact KEN and A-boxes: identification of an aneuploidy-promoting property. Mol Cell Biol. 2005 Jun;25(12):4977-92

Qi M, Yu W, Liu S, Jia H, Tang L, Shen M, Yan X, Saiyin H, Lang Q, Wan B, Zhao S, Yu L. Septin1, a new interaction partner for human serine/threonine kinase aurora-B. Biochem Biophys Res Commun. 2005 Oct 28;336(3):994-1000

Sessa F, Mapelli M, Ciferri C, Tarricone C, Areces LB, Schneider TR, Stukenberg PT, Musacchio A. Mechanism

of Aurora B activation by INCENP and inhibition by hesperadin. Mol Cell. 2005 Apr 29;18(3):379-91

Smith SL, Bowers NL, Betticher DC, Gautschi O, Ratschiller D, Hoban PR, Booton R, Santibáñez-Koref MF, Heighway J. Overexpression of aurora B kinase (AURKB) in primary non-small cell lung carcinoma is frequent, generally driven from one allele, and correlates with the level of genetic instability. Br J Cancer. 2005 Sep 19;93(6):719-29

Sorrentino R, Libertini S, Pallante PL, Troncone G, Palombini L, Bavetsias V, Spalletti-Cernia D, Laccetti P, Linardopoulos S, Chieffi P, Fusco A, Portella G. Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation. J Clin Endocrinol Metab. 2005 Feb;90(2):928-35

Stewart S, Fang G. Destruction box-dependent degradation of aurora B is mediated by the anaphase-promoting complex/cyclosome and Cdh1. Cancer Res. 2005 Oct 1;65(19):8730-5

Chieffi P, Cozzolino L, Kisslinger A, Libertini S, Staibano S, Mansueto G, De Rosa G, Villacci A, Vitale M, Linardopoulos S, Portella G, Tramontano D. Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation. Prostate. 2006 Feb 15;66(3):326-33

Knowlton AL, Lan W, Stukenberg PT. Aurora B is enriched at merotelic attachment sites, where it regulates MCAK. Curr Biol. 2006 Sep 5;16(17):1705-10

Sistayanarain A, Tsuneyama K, Zheng H, Takahashi H, Nomoto K, Cheng C, Murai Y, Tanaka A, Takano Y. Expression of Aurora-B kinase and phosphorylated histone H3 in hepatocellular carcinoma. Anticancer Res. 2006 Sep-Oct;26(5A):3585-93

Vader G, Medema RH, Lens SM. The chromosomal passenger complex: guiding Aurora-B through mitosis. J Cell Biol. 2006 Jun 19;173(6):833-7

Vischioni B, Oudejans JJ, Vos W, Rodriguez JA, Giaccone G. Frequent overexpression of aurora B kinase, a novel drug target, in non-small cell lung carcinoma patients. Mol Cancer Ther. 2006 Nov;5(11):2905-13

Warner SL, Gray PJ, Von Hoff DD. Tubulin-associated drug targets: Aurora kinases, Polo-like kinases, and others. Semin Oncol. 2006 Aug;33(4):436-48

Fu J, Bian M, Jiang Q, Zhang C. Roles of Aurora kinases in mitosis and tumorigenesis. Mol Cancer Res. 2007 Jan;5(1):1-10

Ikezoe T, Yang J, Nishioka C, Tasaka T, Taniguchi A, Kuwayama Y, Komatsu N, Bandobashi K, Togitani K, Koeffler HP, Taguchi H. A novel treatment strategy targeting Aurora kinases in acute myelogenous leukemia. Mol Cancer Ther. 2007 Jun;6(6):1851-7

Kaur H, Stiff AC, Date DA, Taylor WR. Analysis of mitotic phosphorylation of borealin. BMC Cell Biol. 2007 Jan 22;8:5

Knauer SK, Mann W, Stauber RH. Survivin's dual role: an export's view. Cell Cycle. 2007 Mar 1;6(5):518-21

Sakita-Suto S, Kanda A, Suzuki F, Sato S, Takata T, Tatsuka M. Aurora-B regulates RNA methyltransferase NSUN2. Mol Biol Cell. 2007 Mar;18(3):1107-17

Sumara I, Quadroni M, Frei C, Olma MH, Sumara G, Ricci R, Peter M. A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression



and completion of cytokinesis in human cells. Dev Cell. 2007 Jun;12(6):887-900

Wheatley SP, Barrett RM, Andrews PD, Medema RH, Morley SJ, Swedlow JR, Lens SM. Phosphorylation by aurora-B negatively regulates survivin function during mitosis. Cell Cycle. 2007 May 15;6(10):1220-30

Zachos G, Black EJ, Walker M, Scott MT, Vagnarelli P, Earnshaw WC, Gillespie DA. Chk1 is required for spindle checkpoint function. Dev Cell. 2007 Feb;12(2):247-60

Zeng WF, Navaratne K, Prayson RA, Weil RJ. Aurora B expression correlates with aggressive behaviour in glioblastoma multiforme. J Clin Pathol. 2007 Feb;60(2):218-21

Andersen CB, Wan Y, Chang JW, Riggs B, Lee C, Liu Y, Sessa F, Villa F, Kwiatkowski N, Suzuki M, Nallan L, Heald R, Musacchio A, Gray NS. Discovery of selective aminothiazole aurora kinase inhibitors. ACS Chem Biol. 2008 Mar 20;3(3):180-92

Emanuele MJ, Lan W, Jwa M, Miller SA, Chan CS, Stukenberg PT. Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly. J Cell Biol. 2008 Apr 21;181(2):241-54

Gautschi O, Heighway J, Mack PC, Purnell PR, Lara PN Jr, Gandara DR. Aurora kinases as anticancer drug targets. Clin Cancer Res. 2008 Mar 15;14(6):1639-48

Girdler F, Sessa F, Patercoli S, Villa F, Musacchio A, Taylor S. Molecular basis of drug resistance in aurora kinases. Chem Biol. 2008 Jun;15(6):552-62

Mountzios G, Terpos E, Dimopoulos MA. Aurora kinases as targets for cancer therapy. Cancer Treat Rev. 2008 Apr;34(2):175-82

Tanaka S, Arii S, Yasen M, Mogushi K, Su NT, Zhao C, Imoto I, Eishi Y, Inazawa J, Miki Y, Tanaka H. Aurora kinase B is a predictive factor for the aggressive recurrence of hepatocellular carcinoma after curative hepatectomy. Br J Surg. 2008 May;95(5):611-9

Fu J, Bian M, Liu J, Jiang Q, Zhang C. A single amino acid change converts Aurora-A into Aurora-B-like kinase in terms of partner specificity and cellular function. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):6939-44

Yasen M, Mizushima H, Mogushi K, Obulhasim G, Miyaguchi K, Inoue K, Nakahara I, Ohta T, Aihara A, Tanaka S, Arii S, Tanaka H. Expression of Aurora B and alternative variant forms in hepatocellular carcinoma and adjacent tissue. Cancer Sci. 2009 Mar;100(3):472-80

López-Saavedra A, Herrera LA. The role of alternative mRNA splicing in chromosome instability. Mutat Res. 2010 Dec;705(3):246-51

Gully CP, Velazquez-Torres G, Shin JH, Fuentes-Mattei E, Wang E, Carlock C, Chen J, Rothenberg D, Adams HP, Choi HH, Guma S, Phan L, Chou PC, Su CH, Zhang F, Chen JS, Yang TY, Yeung SC, Lee MH. Aurora B kinase phosphorylates and instigates degradation of p53. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):E1513-22

Yoshida A, Zokumasu K, Wano Y, Yamauchi T, Imamura S, Takagi K, Kishi S, Urasaki Y, Tohyama K, Ueda T. Marked upregulation of Survivin and Aurora-B kinase is associated with disease progression in the myelodysplastic syndromes. Haematologica. 2012 Sep;97(9):1372-9

This article should be referenced as such:

Yeung SCJ. AURKB (aurora kinase B). Atlas Genet Cytogenet Oncol Haematol. 2014; 18(12):872-878.

gene section · 2016. 6. 20. · aurkb (aurora kinase b) yeung scj atlas genet cytogenet oncol...

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