Bub2s

Bub2s refers to a family of spindle checkpoint-related GTPase-activating proteins that regulate the mitotic exit network in yeast and related fungi. The best-characterized member is Bub2 of Saccharomyces cerevisiae. Bub2 forms a stable complex with Bfa1 and localizes to spindle pole bodies (SPBs). In this complex, Bub2 provides the GAP activity toward Tem1, a small GTPase. When Tem1 is GDP-bound, the mitotic exit network (MEN) remains inactive, postponing mitotic exit. Activation of MEN requires Tem1 to bind GTP, a process promoted by the GEF-like activity of Lte1 and by relief of Bub2-Bfa1 GAP activity through phosphorylation.

Regulatory interactions further involve Cdc5, a polo-like kinase, which phosphorylates Bub2 and Bfa1 to reduce GAP activity and enable Tem1 activation. Kin4 kinase acts to enforce the spindle position checkpoint by promoting retention of Bub2-Bfa1 at SPBs when spindle orientation is defective, thereby delaying MEN. The localization and activity of the Bub2-Bfa1 complex are dynamic, changing as cells progress through mitosis in response to spatial cues from the spindle.

Impact and evolution: Mutations or deletions that disrupt Bub2 or Bfa1 can alter the timing of mitotic exit and lead to spindle defects or chromosome missegregation. Bub2 and Bfa1 homologs are conserved in many fungi, illustrating a broadly similar role in coordinating spindle position with mitotic progression, though exact regulatory inputs can vary among species. In yeast research, Bub2s are central to understanding how cells couple spindle positioning to the timing of mitotic exit.