posted on 2013-12-10, 11:23authored byBalca R. Mardin, Mayumi Isokane, Marco R. Cosenza, Alwin Kräemer, Jan Ellenberg, Andrew M. Fry, Elmar Schiebel
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.
This work was supported by financial support of the SFB1036. A.M.F. acknowledges support from the Association of International Cancer Research (AICR), the Wellcome Trust, and Cancer Research UK.
Developmental Cell, 2013, 25 (3), pp. 229-240
/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Biochemistry