Tre2Bub2Cdc16

Tre2Bub2Cdc16 is a multicomponent regulatory complex described in eukaryotic cell-cycle control, named for its constituent proteins Tre2, Bub2, and Cdc16. The best-characterized aspect involves the Bub2-Cdc16 subcomplex, which forms a GTPase-activating protein (GAP) for Tem1, a small GTPase that drives the mitotic exit network (MEN) in budding yeast. By stimulating Tem1 GTP hydrolysis, Bub2-Cdc16 helps maintain Tem1 in an inactive state, delaying mitotic exit until the spindle is properly positioned.

Cdc16 is also a core subunit of the anaphase-promoting complex/cyclosome (APC/C), linking cell-cycle progression with ubiquitin-mediated proteolysis. The precise role of the Tre2 component within the complex is less well defined; some evidence suggests it may influence complex localization or stability, but its exact biochemical function in this context remains under investigation.

Localization studies indicate the complex associates with key mitotic structures such as spindle pole bodies and the bud neck, consistent with a checkpoint-like function that coordinates spindle orientation with mitotic progression. Regulation is mediated by cell-cycle kinases, including Cdc5 (a Polo-like kinase) and Cdk1, and by interactions with other MEN components, such as Bfa1. Disruption or misregulation of the complex can lead to delayed exit from mitosis, abnormal spindle positioning, and cytokinesis defects.

In summary, Tre2Bub2Cdc16 is viewed as a regulatory module at the intersection of the MEN and APC/C pathways, integrating spindle-position signals with mitotic exit control. The precise contribution of the Tre2 subunit and its conservation across species require further study.