Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres

Abstract

Shugoshin (Sgo) is a conserved centromeric protein. Mammalian Sgo1 collaborates with protein phosphatase 2A (PP2A) to protect mitotic cohesin from the prophase dissociation pathway. Although another shugoshin-like protein, Sgo2, is required for the centromeric protection of cohesion in germ cells, its precise molecular function remains largely elusive. We demonstrate that hSgo2 plays a dual role in chromosome congression and centromeric protection of cohesion in HeLa cells, while the latter function is exposed only in perturbed mitosis. These functions partly overlap with those of Aurora B, a kinase setting faithful chromosome segregation. Accordingly, we identified the phosphorylation of hSgo2 by Aurora B at the N-terminal coiled-coil region and the middle region, and showed that these phosphorylations separately promote binding of hSgo2 to PP2A and MCAK, factors required for centromeric protection and chromosome congression, respectively. Furthermore, these phosphorylations are essential for localizing PP2A and MCAK to centromeres. This mechanism seems applicable to germ cells as well. Thus, our study identifies Sgo2 as a hitherto unknown crucial cellular substrate of Aurora B in mammalian cells.[Keywords: Chromosome segregation; centromere; shugoshin; Aurora B; MCAK; PP2A] Supplemental material is available at http://www.genesdev.org.

Oocyte ageing and its cellular basis

“…Cohesion becomes lost along the sister chromatid arms at late prometaphase by nonproteolytic events involving protein phosphorylation of a mitotic cohesin protein. Cohesion at centromeres is retained involving activity of proteins like shugoshin (the Japanese name for "guardian spirit"), Aurora kinase B and phosphatase PP2A that prevent critical protein phosphorylation of the kleisin cohesins (Ishiguro et al, 2010;Tanno et al, 2010). Cohesion at centromeres is only lost after the SAC is satisfied, and no more MCC is produced.…”

“…Ishiguro et al, 2010;Garcia-Cruiz et al, 2010). The targeting of shugoshin itself that is necessary to recruit PP2A to the centromeres is involving Aurora kinase B and causes also recruitment of mitotic centromere associated kinase (MCAK) to centromeres, which is a depolymerase resolving improper microtubule attachments (Tanno et al, 2010).…”

Sgo1 recruits PP2A to chromosomes to ensure sister chromatid bi-orientation in mitosis

“…Shugoshins protect centromeric cohesin by recruiting protein phosphatase 2A (PP2A), which removes phosphates from cohesin and thereby inhibits its cleavage (Brar et al, 2006;Ishiguro et al, 2010;Katis et al, 2010;Kitajima et al, 2006;Riedel et al, 2006;Tang et al, 2006;Tanno et al, 2010). Similarly, during prophase, shugoshins recruit PP2A to dephosphorylate sororin, allowing it to block cohesin removal by Wapl (Liu et al, 2013;Nishiyama et al, 2010).…”

Visualize Dynamic Chromosome

“…The detailed of the whole mechanism is still almost unclear. However, number of molecules which involved in the mitotic events have been identified such as SMC proteins, including condensin (chromosome condensation), cohesion (chromosome cohesion of replicated chromosomes) (Swedlow and Hirano, 2003), NuMA protein for spindle pole formation (Chang et al, 2009;Haren et al, 2009;Silk et al, 2009;Torres et al, 2010), nuclear lamins (Moir et al, 2000), aurora kinases in centromere function (Tanno et al, 2006;Meyer et al, 2010;Tanno et al, 2010), shugoshin and protein protein phosphatase 2A in chromosome cohesion (Kitajima et al, 2006;Tanno et al, 2010), cdk1 in chromosome condensation, chromosome biorientation (Tsukahara et al, 2010), cyclin B, cdc2, cdc25 in chromosome condensation (Masui, 1974;Draetta and Beach, 1988;Dunphy et al, 1988;Kumagai and Dunphy, 1992), Polo and Rho in cytokinesis (Burkard et al, 2009;Wolfe et al, 2009;Li et al, 2010) and many other proteins. Chromosome dynamic consists of such number of various elements.…”