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

14 Mar 2016Journal of Cell Biology

DOI : 10.1083/jcb.201408089

Authors

Mayumi Isokane, Thomas Walter, Robert Mahen, Bianca Nijmeijer, Jean-Karim Hériché, Kota Miura, Stefano Maffini, Miroslav Penchev Ivanov, Tomoya S. Kitajima, Jan-Michael Peters, Jan Ellenberg

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.

Members

THOMAS WALTER

Directeur de recherche Mines Paris Tech