High impact information on BFA1

• PP2A(Cdc55) downregulation also promotes phosphorylation of Bfa1, contributing to activation of the "mitotic exit network" that sustains Cdc14 as Cdk activity declines [1].
• How the Bfa1/Bub2 complex is regulated is not well understood [2].
• During most of the cell cycle, Tem1 function is antagonized by a GTPase-activating protein complex, Bfa1/Bub2 [2].
• Cdc5 phosphorylates Bfa1 and acts to antagonize Bfa1 function to promote mitotic exit [2].
• Bfa1 is regulated by multiple cell cycle checkpoints [2].

Biological context of BFA1

• Both Bfa1 and Bub2 localize to spindle poles, and overexpression of Bfa1 arrests the cell cycle in anaphase [3].
• We propose that Bfa1/Bub2 checkpoint pathway functions as a universal checkpoint in G2/M that prevents CDK inactivation in response to cell-cycle delay in G2/M [4].
• The C-terminal 184 amino acids of Bfa1p (Bfa1-D8(391-574)) contained the entire capacity of Bfa1p to generate mitotic arrest in response to spindle damage, spindle misorientation, and DNA damage [5].
• In addition, the viability of cdc5-2 delta bfa1 cells was not reduced by BFA1(E438K), suggesting that Cdc5p also regulates Bfa1p to activate mitotic exit by other mechanism(s), besides phosphorylation [6].
• Thus, in vivo inactivation of Bfa1-Bub2 by Cdc5 would have a positive regulatory effect by increasing levels of Tem1-GTP so stimulating exit from mitosis [7].

Anatomical context of BFA1

• Thus, SPBs are able to sense cytoplasmic microtubule properties and regulate the Bfa1p-Bub2p GAP accordingly [8].

Physical interactions of BFA1

• Coimmunoprecipitation and in vitro binding studies indicate that Bfa1 binds strongly to Tem1 independently of Bub2 [9].
• The Bfa1/Bub2 GAP complex comprises a universal checkpoint required to prevent mitotic exit [4].
• We have isolated a novel Bfa1p interacting protein named Ibd2p in the budding yeast Saccharomyces cerevisiae [10].
• Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints [2].

Regulatory relationships of BFA1

• This effect is Bfa1 dependent and can be suppressed by high Tem1 levels [11].
• These data indicate that Cdc14p activates the MEN in early anaphase but later inactivates it through Bfa1p dephosphorylation and so restricts MEN activity to a short period in anaphase [12].

Other interactions of BFA1

• Here, we have demonstrated that introduction of bfa1 Delta suppresses the growth defects associated with the cdc5-1 mutation significantly better than that of bub2 Delta, suggesting that Bfa1 may have a previously uncharacterized role in this pathway [9].
• In the spindle checkpoint pathway, this is accomplished through Bfa1/Bub2, a heteromeric GTPase-activating protein (GAP) that inhibits Clb degradation by keeping the G protein Tem1 inactive [3-5] [4].
• We also found that the delay in mitotic exit in mutants with misoriented spindles depended on BUB2 and BFA1, but not on MAD2 [4].
• Following spindle checkpoint activation, the cell cycle phosphorylation of Bfa1 and Lte1 is protracted and some species are accentuated [13].
• Regulation of the Bfa1p-Bub2p complex at spindle pole bodies by the cell cycle phosphatase Cdc14p [12].

References