BTB-1: A Small Molecule Inhibitor of the Mitotic Motor Protein Kif18A

被引：52

作者：

Catarinella, Mario ^{[1
]}

Gruener, Tamara ^{[2
]}

Strittmatter, Tobias ^{[1
]}

Marx, Andreas ^{[1
]}

Mayer, Thomas U. ^{[1
]}

机构：

[1] Univ Konstanz, Konstanz Res Sch Chem Biol, D-78457 Constance, Germany

[2] London Res Inst, Lincolns Inn Fields Labs, London WC2A 3PX, England

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2009年 / 48卷 / 48期

关键词：

antiproliferation; enzymes; inhibitors; mitosis; molecular motors; KINESIN EG5; CHROMOSOME ALIGNMENT; CELL-DIVISION; SPINDLE; POLO-LIKE-KINASE-1; MICROTUBULES;

D O I：

10.1002/anie.200904510

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Turning the motor off: A malachite green based assay leads to the identification of BTB-1 (see picture), the first small-molecule inhibitor of the mitotic motor protein Kif18A. BTB-1 reversibly inhibits the ATPase activity of the recombinant motor domain of Kif18A in vitro (see picture; red microtubules, blue/black structure = Kif18A) and will be a valuable tool to dissect the mechanochemical properties of Kif18A. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：9072 / 9076

页数：5

共 16 条

[1]

DeBonis S, 2004, MOL CANCER THER, V3, P1079

[2] Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores [J].

Ditchfield, C ;

Johnson, VL ;

Tighe, A ;

Ellston, R ;

Haworth, C ;

Johnson, T ;

Mortlock, A ;

Keen, N ;

Taylor, SS .

JOURNAL OF CELL BIOLOGY, 2003, 161 (02) :267-280

[3] Plus end-specific depolymerase activity of Kip3, a kinesin-8 protein, explains its role in positioning the yeast mitotic spindle [J].

Gupta, Mohan L., Jr. ;

Carvalho, Pedro ;

Roof, David M. ;

Pellman, David .

NATURE CELL BIOLOGY, 2006, 8 (09) :913-U33

[4] HR22C16: A potent small-molecule probe for the dynamics of cell division [J].

Hotha, S ;

Yarrow, JC ;

Yang, JG ;

Garrett, S ;

Renduchintala, KV ;

Mayer, TU ;

Kapoor, TM .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (21) :2379-2382

[5] The small-molecule inhibitor BI 2536 reveals novel insights into mitotic roles of polo-like kinase 1 [J].

Lenart, Peter ;

Petronczki, Mark ;

Steegmaier, Martin ;

Di Fiore, Barbara ;

Lipp, Jesse J. ;

Hoffmann, Matthias ;

Rettig, Wolfgang J. ;

Kraut, Norbert ;

Peters, Jan-Michael .

CURRENT BIOLOGY, 2007, 17 (04) :304-315

[6] Evidence that monastrol is an allosteric inhibitor of the mitotic kinesin Eg5 [J].

Maliga, Z ;

Kapoor, TM ;

Mitchison, TJ .

CHEMISTRY & BIOLOGY, 2002, 9 (09) :989-996

[7] Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen [J].

Mayer, TU ;

Kapoor, TM ;

Haggarty, SJ ;

King, RW ;

Schreiber, SL ;

Mitchison, TJ .

SCIENCE, 1999, 286 (5441) :971-974

[8] The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression [J].

Mayr, Monika I. ;

Huemmer, Stefan ;

Bormann, Jenny ;

Gruener, Tamara ;

Adio, Sarah ;

Woehlke, Guenther ;

Mayer, Thomas U. .

CURRENT BIOLOGY, 2007, 17 (06) :488-498

[9] Probing cell-division phenotype space and Polo-like kinase function using small molecules [J].

Peters, Ulf ;

Cherian, Joseph ;

Kim, Jeffrey H. ;

Kwok, Benjamin H. ;

Kapoor, Tarun M. .

NATURE CHEMICAL BIOLOGY, 2006, 2 (11) :618-626

[10] Inhibition of polo-like kinase 1 by blocking Polo-box domain-dependent protein-protein interactions [J].

Reindl, Wolfgang ;

Yuan, Juping ;

Kraemer, Andrea ;

Strebhardt, Klaus ;

Berg, Thorsten .

CHEMISTRY & BIOLOGY, 2008, 15 (05) :459-466

← 1 2 →