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Title: EGF-induced centrosome separation promotes mitotic progression and cell survival
Authors: Mardin, Balca R.
Isokane, Mayumi
Cosenza, Marco R.
Kräemer, Alwin
Ellenberg, Jan
Fry, Andrew M.
Schiebel, Elmar
First Published: 2-May-2013
Publisher: Elsevier (Cell Press)
Citation: Developmental Cell, 2013, 25 (3), pp. 229-240
Abstract: Timely and accurate assembly of the mitotic spindle is critical for the faithful segregation of chromosomes, and centrosome separation is a key step in this process. The timing of centrosome separation varies dramatically between cell types; however, the mechanisms responsible for these differences and its significance are unclear. Here, we show that activation of epidermal growth factor receptor (EGFR) signaling determines the timing of centrosome separation. Premature separation of centrosomes decreases the requirement for the major mitotic kinesin Eg5 for spindle assembly, accelerates mitosis, and decreases the rate of chromosome missegregation. Importantly, EGF stimulation impacts upon centrosome separation and mitotic progression to different degrees in different cell lines. Cells with high EGFR levels fail to arrest in mitosis upon Eg5 inhibition. This has important implications for cancer therapy because cells with high centrosomal response to EGF are more susceptible to combinatorial inhibition of EGFR and Eg5.
DOI Link: 10.1016/j.devcel.2013.03.012
ISSN: 1534-5807
eISSN: 1878-1551
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2013 Elsevier Inc. Deposited with reference to the publisher’s open access archiving policy.
Appears in Collections:Published Articles, Dept. of Biochemistry

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