Tem1GTP

Tem1-GTP refers to the GTP-bound active form of Tem1, a Ras-like small GTPase in the budding yeast Saccharomyces cerevisiae. Tem1-GTP sits at the core of the mitotic exit network (MEN), acting as a molecular switch that links spindle position and cell-cycle progression to the completion of mitosis.

Tem1 localizes to the spindle pole bodies (SPBs) and cycles between GDP- and GTP-bound states. In late mitosis, Tem1-GTP promotes the activation of the MEN kinase cascade, leading to activation of the Cdc14 phosphatase. Cdc14 release from the nucleolus initiates a program of mitotic exit, including cyclin degradation, chromosome segregation completion, and cytokinesis.

Regulation of Tem1-GTP involves opposing activities at the SPBs. Bub2-Bfa1 forms a GTPase-activating protein (GAP) complex that maintains Tem1 in the GDP-bound (inactive) state, particularly on the mother SPB. In contrast, Lte1, a putative guanine nucleotide exchange factor (GEF) located in the cytoplasm of the daughter cell, promotes exchange of GDP for GTP on Tem1, favoring Tem1-GTP formation when the SPB enters the bud. The spatial separation of these regulators ensures that MEN activation occurs only after proper spindle orientation. Kin4 kinase activity can further inhibit Tem1 at the mother SPB, reinforcing asymmetry and delaying MEN activation if necessary.

Genetic and biochemical studies show that Tem1 is essential for timely mitotic exit; tem1 mutants often fail to exit mitosis properly, remaining arrested in late stages. Tem1-GTP remains a central symbol of the MEN, integrating spindle position cues with cell-cycle progression.