A functional genomic screen identifies a role for TAO1 kinase in spindle-checkpoint signalling

Draviam, V. M., Stegmeier, F., Nalepa, G., Sowa, M. E., Chen, J., Liang, A., Hannon, G. J., Sorger, P. K., Harper, J. W., Elledge, S. J. (May 2007) A functional genomic screen identifies a role for TAO1 kinase in spindle-checkpoint signalling. Nature Cell Biology, 9 (5). pp. 556-564. ISSN 1465-7392

Abstract

Defects in chromosome-microtubule attachment trigger spindle-checkpoint activation and delay mitotic progression(1,2). How microtubule attachment is sensed and integrated into the steps of checkpoint-signal amplification is poorly understood. In a functional genomic screen targeting human kinases and phosphatases, we identified a microtubule affinity-regulating kinase kinase, TAO1 (also known as MARKK) as an important regulator of mitotic progression, required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 interacts with the checkpoint kinase BubR1 and promotes enrichment of the checkpoint protein Mad2 at sites of defective attachment, providing evidence for a regulatory step that precedes the proposed Mad2-Mad1 dependent checkpoint- signal amplification step(3). We propose that the dual functions of TAO1 in regulating microtubule dynamics and checkpoint signalling may help to coordinate the establishment and monitoring of correct congression of chromosomes, thereby protecting genomic stability in human cells.

Item Type: Paper
Uncontrolled Keywords: KINETOCHORE LOCALIZATION CHROMOSOME CONGRESSION MAMMALIAN-CELLS PROTEIN-KINASE CENP-E MAD2 MITOSIS BUB1 P38 ACTIVATION
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > microtubule
organs, tissues, organelles, cell types and functions > organelles, types and functions > mitosis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein phosphatase
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: CSHL Librarian
Date: May 2007
Date Deposited: 30 Nov 2011 20:59
Last Modified: 02 Dec 2016 15:46
Related URLs:
URI: https://repository.cshl.edu/id/eprint/23002

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