Examining the involvement of Slx5 in the apoptotic response to chronic activation of the spindle assembly checkpoint

WOS: 000471268100004PubMed ID: 31320817Microtubule-targeting agents represent one of the most successful groups of anticancer drugs used in cancer therapy today. These drugs induce a prolonged mitotic arrest through chronic spindle assembly checkpoint (SAC) activation. Apoptosis, an outcome of the prolonged mitotic arrest, is the main mechanism by which these anticancer drugs kill cancer cells. However, not much is known about the mechanism that directs chronic SAC activation to apoptosis among other possible outcomes. The aim of this study is to investigate whether Slx5, a sumo-targeted ubiquitin E3 ligase, is involved in directing chronic SAC activation to apoptosis. We show that chronic SAC activation triggered by a 10-h nocodazole incubation leads to a prolonged mitotic arrest in the slx5 Delta strain similar to wild type (WT). However, the proportion of cells displaying apoptotic features such as nuclear fragmentation, DNA fragmentation, and reactive oxygen species (ROS) production were increased more in the WT strain during the chronic SAC activation compared to slx5 Delta, indicating that SLx5 may be involved in the chronic SAC-activation-apoptosis relation. We also showed that the possible role of Slx5 in the chronic SAC activation-apoptosis association was not through ubiquitin dependent degradation of 3 apoptosis-related and sumoylated candidate proteins.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [115Z157]We would like to thank Dr. Daniel J. Burke (North Carolina State University, College of Sciences, Department of Biological Sciences) for generously sending us the wild type TAP-tagged S. cerevisiae strains. This study was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) with the project number: 115Z157