BUB1 and SURVIVIN proteins are not degraded after a prolonged mitosis and accumulate in the nuclei of HCT116 cells.
Spindle poisons activate the spindle assembly checkpoint and prevent mitotic exit until cells die or override the arrest. Several studies have focused on spindle poison-mediated cell death, but less is known about consequences in cells that survive a mitotic arrest. During mitosis, proteins such as CYCLIN B, SECURIN, BUB1 and SURVIVIN are degraded in order to allow mitotic exit, and these proteins are maintained at low levels in the next interphase. In contrast, exit from a prolonged mitosis depends only on degradation of CYCLIN B; it is not known whether the levels of other proteins decrease or remain high. Here, we analyzed the levels and localization of the BUB1 and SURVIVIN proteins in cells that escaped from a paclitaxel-mediated prolonged mitosis. We compared cells with a short arrest (HCT116 cells) with cells that spent more time in mitosis (HT29 cells) after paclitaxel treatment. BUB1 and SURVIVIN were not degraded and remained localized to the nuclei of HCT116 cells after a mitotic arrest. Moreover, BUB1 nuclear foci were observed; BUB1 did not colocalize with centromere proteins. In HT29 cells, the levels of BUB1 and SURVIVIN decreased during the arrest, and these proteins were not present in cells that reached the next interphase. Using time-lapse imaging, we observed morphological heterogeneity in HCT116 cells that escaped from the arrest; this heterogeneity was due to the cytokinesis-like mechanism by which the cells exited mitosis. Thus, our results show that high levels of BUB1 and SURVIVIN can be maintained after a mitotic arrest, which may promote resistance to cell death.
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas - Universidad Nacional Autónoma de México; Insituto Nacional de Cancerología , México City 14080, Mexico.
Marco A
MA
Andonegui-Elguera
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas - Universidad Nacional Autónoma de México; Insituto Nacional de Cancerología , México City 14080, Mexico.
Rodrigo E
RE
Cáceres-Gutiérrez
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas - Universidad Nacional Autónoma de México; Insituto Nacional de Cancerología , México City 14080, Mexico.
Fernando
F
Luna-Maldonado
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas - Universidad Nacional Autónoma de México; Insituto Nacional de Cancerología , México City 14080, Mexico.
Alejandro
A
López-Saavedra
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas - Universidad Nacional Autónoma de México; Insituto Nacional de Cancerología , México City 14080, Mexico.
José
J
Díaz-Chávez
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas - Universidad Nacional Autónoma de México; Insituto Nacional de Cancerología , México City 14080, Mexico.
Fernanda
F
Cisneros-Soberanis
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas - Universidad Nacional Autónoma de México; Insituto Nacional de Cancerología , México City 14080, Mexico.
Diddier
D
Prada
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas - Universidad Nacional Autónoma de México; Insituto Nacional de Cancerología , México City 14080, Mexico.
Julia
J
Mendoza-Pérez
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas - Universidad Nacional Autónoma de México; Insituto Nacional de Cancerología , México City 14080, Mexico.
Luis A
LA
Herrera