Bub1 kinase activity drives error correction and mitotic checkpoint control but not tumor suppression

Abstract

Mice expressing a version of Bub1 that lacks kinase activity have increased chromosome segregation errors and aneuploidy but not increased susceptibility to tumors.

STAG2 promotes error correction in mitosis by regulating kinetochore-microtubule attachments

“…S1A), but there was a 40% decrease in the amount of Aurora B kinase localized to centromeres. Instead, Aurora B kinase localized along the length of chromosome arms, similar to the localization observed when Bub1, Sgo1 or Wapl are disrupted (Ricke et al, 2012;Rivera et al, 2012;Haarhuis et al, 2013). This change in localization of Aurora B kinase was mimicked by the distribution of INCENP (Fig.…”

“…Recently, it was demonstrated that Bub1 is required for efficient centromere localization of the CPC (Ricke et al, 2012). One function of Bub1 is to localize the CPC to the centromere by phosphorylating threonine 120 on histone H2A (phospho-H2A T120) (Kawashima et al, 2010;Watanabe, 2010).…”

Dissecting the roles of human BUB1 in the spindle assembly checkpoint

“…Since the discovery of BUB1, the molecular mechanism by which it participates in SAC activation has been a matter of controversy. Studies in mice, budding yeast and fission yeast have shown that BUB1 kinase activity is required for SAC activation (Kawashima et al, 2010;Ricke et al, 2012;Yamaguchi et al, 2003), but this has been contradicted by other studies using the same model organisms (Baker et al, 2009;Fernius and Hardwick, 2007;London and Biggins, 2014;Perera et al, 2007;Rischitor et al, 2007;Warren et al, 2002). Human cell studies have proven equally inconsistentone study proposes that BUB1 directly phosphorylates and inhibits CDC20 (Kang et al, 2008), whereas another shows that a truncated BUB1 protein lacking the kinase domain significantly restored SAC activity to BUB1-depleted cells (Klebig et al, 2009).…”

The dynamic protein Knl1 – a kinetochore rendezvous

“…In addition, neither the presence of KI1 nor KI2 in Knl1 is an absolute requirement for SAC activity or chromosome alignment (Krenn et al, 2012;Yamagishi et al, 2012). Moreover, although the Bub1 TPR domain has been reported to be necessary for optimal Bub1 kinase activity (Krenn et al, 2012;Ricke et al, 2012), a Bub1 TPR mutant that is unable to interact with KI1 does not exhibit altered kinase activity or kinetochore localization of Bub1 (Krenn et al, 2012;Yamagishi et al, 2012), suggesting that it is not the interaction with KI1 per se that promotes catalytic activity. Similarly, KI2 is not necessary for the robust kinetochore recruitment of BubR1 (Yamagishi et al, 2012).…”