A direct interaction between survivin and myosin II is required for cytokinesis

Abstract

An acto-myosin contractile ring, which forms after anaphase onset and is highly regulated in time and space, mediates cytokinesis, the final step of mitosis. The chromosomal passenger complex (CPC), composed of Aurora-B kinase, INCENP, borealin and survivin (also known as BIRC5), regulates various processes during mitosis, including cytokinesis. It is not understood, however, how CPC regulates cytokinesis. We show that survivin binds to non-muscle myosin II (NMII), regulating its filament assembly. Survivin and NMII interact mainly in telophase, and Cdk1 regulates their interaction in a mitotic-phase-specific manner, revealing the mechanism for the specific timing of survivin-NMII interaction during mitosis. The survivin-NMII interaction is indispensable for cytokinesis, and its disruption leads to multiple mitotic defects. We further show that only the survivin homodimer binds to NMII, attesting to the biological importance for survivin homodimerization. We suggest a novel function for survivin in regulating the spatio-temporal formation of the acto-NMII contractile ring during cytokinesis and we elucidate the role of Cdk1 in regulating this process. This article has an associated First Person interview with the first author of the paper.

Cancer therapeutics using survivin BIRC5 as a target: what can we do after over two decades of study?

“…This may also be true for the survivin-ran interaction [29,37]. However, this is not always the case, as most recent studies have indicated that during non-muscle myosin II (NMII)-mediated cytokinesis, only the survivin homodimer binds to NMII, attesting to the biological importance of survivin homodimerization [38]. Nevertheless, it would be intriguing to discover whether the currently identified survivin homodimerization inhibitors such as LQZ-7 and LQZ-7F could also disrupt survivin-Borealin or survivinran interactions.…”

Anti-apoptotic proteins in the autophagic world: an update on functions of XIAP, Survivin, and BRUCE

“…At the molecular level, survivin forms the chromosomal passenger complex (CPC) with inner centromere protein (INCENP), borealin (also known as Dasra), and Aurora B kinase and proper formation (and localization) of the CPC during M phase of the cell cycle are both crucial for the completion of mitosis [64,65]. Interestingly, a recent study revealed that the survivin homodimer interacts with myosin II to regulate cytokinesis [66]. Therefore, survivin is widely accepted as a multi-functions protein, which is capable of inhibiting caspase-dependent and -independent apoptosis through both direct and indirect modulations and promoting mitosis through formation of the CPC in cancer cells.…”

Comparative Analysis of the Roles of Non-muscle Myosin-IIs in Cytokinesis in Budding Yeast, Fission Yeast, and Mammalian Cells

“…Thus, RhoA is required for AMR assembly in mammalian cells ( Figure 4B; Basant and Glotzer, 2018;Verma et al, 2019). The chromosomal passenger complex (CPC), including its components Aurora B and survivin, appears to regulate IIB localization during the abscission stage ( Figure 4B; Kondo et al, 2013;Babkoff et al, 2019). Similar to Myo1 in budding yeast (Fang et al, 2010), the central region of the IIA tail (residues 834-1,632) is required for its localization to the division site (Figure 1), but its tethering factor at the division site remains unknown (Beach and Egelhoff, 2009).…”