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

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J Cell Biol-2016-Isokane-647-59.pdfPublished version2.83 MBAdobe PDFDownload
Title: ARHGEF17 is an essential spindle assembly checkpoint factor that targets Mps1 to kinetochores
Author(s): Isokane, M
Walter, T
Mahen, R
Nijmeijer, B
Hériché, J-K
Miura, K
Maffini, S
Ivanov, MP
Kitajima, TS
Peters, J-M
Ellenberg, J
Item Type: Journal Article
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.
Publication Date: 7-Mar-2016
Date of Acceptance: 11-Feb-2016
URI: http://hdl.handle.net/10044/1/40098
DOI: http://dx.doi.org/10.1083/jcb.201408089
ISSN: 0021-9525
Publisher: Rockefeller University Press
Start Page: 647
End Page: 659
Journal / Book Title: The Journal of Cell Biology
Volume: 212
Issue: 6
Copyright Statement: This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
Keywords: Developmental Biology
06 Biological Sciences
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Physics
Photonics
Faculty of Natural Sciences



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