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ARHGEF17 is an essential spindle assembly checkpoint factor that targets Mps1 to kinetochores.


ABSTRACT: To prevent genome instability, mitotic exit is delayed until all chromosomes are properly attached to the mitotic spindle by the spindle assembly checkpoint (SAC). In this study, we characterized the function of ARHGEF17, identified in a genome-wide RNA interference screen for human mitosis genes. Through a series of quantitative imaging, biochemical, and biophysical experiments, we showed that ARHGEF17 is essential for SAC activity, because it is the major targeting factor that controls localization of the checkpoint kinase Mps1 to the kinetochore. This mitotic function is mediated by direct interaction of the central domain of ARHGEF17 with Mps1, which is autoregulated by the activity of Mps1 kinase, for which ARHGEF17 is a substrate. This mitosis-specific role is independent of ARHGEF17's RhoGEF activity in interphase. Our study thus assigns a new mitotic function to ARHGEF17 and reveals the molecular mechanism for a key step in SAC establishment.

SUBMITTER: Isokane M 

PROVIDER: S-EPMC4792069 | biostudies-other | 2016 Mar

REPOSITORIES: biostudies-other

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ARHGEF17 is an essential spindle assembly checkpoint factor that targets Mps1 to kinetochores.

Isokane Mayumi M   Walter Thomas T   Mahen Robert R   Nijmeijer Bianca B   Hériché Jean-Karim JK   Miura Kota K   Maffini Stefano S   Ivanov Miroslav Penchev MP   Kitajima Tomoya S TS   Peters Jan-Michael JM   Ellenberg Jan J  

The Journal of cell biology 20160307 6


To prevent genome instability, mitotic exit is delayed until all chromosomes are properly attached to the mitotic spindle by the spindle assembly checkpoint (SAC). In this study, we characterized the function of ARHGEF17, identified in a genome-wide RNA interference screen for human mitosis genes. Through a series of quantitative imaging, biochemical, and biophysical experiments, we showed that ARHGEF17 is essential for SAC activity, because it is the major targeting factor that controls localiz  ...[more]

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