The 14-3-3 protein Bmh1 functions in the spindle position checkpoint by breaking Bfa1 asymmetry at yeast centrosomes

Abstract

Phosphorylation of Bfa1 by Kin4 creates a docking site on Bfa1 for the 14-3-3 family protein Bmh1, which in turn weakens Bfa1–centrosome association and promotes symmetric Bfa1 localization to engage the spindle position checkpoint.

LTE1 promotes exit from mitosis by multiple mechanisms

“…Cells lacking KIN4 or RTS1 produce fewer multinucleate cells, indicating that SPOC activity is partially retained. In contrast, swe1∆ or bmh1Δ mutants, which were previously reported to harbor mild checkpoint defects (Caydasi et al ., 2014; Moore et al ., 2010), formed few if any multinucleate cells in our experimental setup (Figure 2A). …”

Fin1-PP1 Helps Clear Spindle Assembly Checkpoint Protein Bub1 from Kinetochores in Anaphase

“…Bmh1 may play Fin1-independent roles, as Bmh1 binds to many proteins (Kakiuchi et al, 2007; van Heusden, 2009). For instance, Bmh1 regulates mitotic exit through its interaction with Bfa1, a negative regulator of mitotic exit network (Caydasi et al, 2014). The FEAR pathway regulates anaphase onset through multiple mechanisms in addition to Fin1.…”

The Centrosome and Its Duplication Cycle

“…Once the GAP is inhibited, the intrinsic GTP exchange activity of Tem1 family GTPases (Furge et al 1998;Geymonat et al 2003) and Schiebel 2005). Kin4 phosphorylation of Bfa1 both blocks its ability to be inhibited through Polo Cdc5 phosphorylation and promotes docking of 14-3-3 proteins to drive Bfa1 turnover at SPBs (Caydasi and Pereira 2009;Caydasi et al 2014). Bfa1 phosphorylation by Kin4, therefore, locks MEN signaling in the off state.…”

“…Spindle misalignment errors that result in the retention of both SPBs in the mother cell place these two SPBs in the zone of high Kin4 activity that drives Kin4 onto both SPBs to block mitotic exit. If one SPB eventually enters the bud, Kin4 activity will be inhibited on that SPB bud by Lte1 to promote Kin4 departure and so drive MEN activation from this SPB bud (Bertazzi et al 2011;Falk et al 2011;Caydasi et al 2014). …”