Figure 2

Cell cycle profile of Mps1 and its control by degradation. The top panel shows the cell cycle profile of hMps1 protein levels (broken grey line) and protein kinase activity (solid black line), adapted from the data of Hogg et al., 1994 [64]. After a sharp peak of hMps1 activity at G1/S that is not accompanied by a rise in whole cell protein levels, both protein and activity peak in mitosis. After completing its function in the spindle checkpoint, Mps1 is targeted for degradation at mitotic exit by both Cdc20- and Cdh1-associated APC/C complexes through the hMps1 D-box. Cdh1-dependent hMps1 degradation keeps cytoplasmic hMps1 levels low in G1, while OAZ targets the centrosomal pool of Mps1 for degradation through the MDS. Phosphorylation of T468 within the MDS transiently suppresses OAZ-mediated degradation, allowing accumulation of a centrosomal pool coincident with centrosome duplication. The lower panel shows a schematic of the 853 amino acid hMps1 protein indicating the positions of the D-box (amino acids 256-263) and MDS (amino acids 420-507) in yellow as the binding sites for Cdh1/Cdc20 (blue) and OAZ (red), respectively, and the kinase domain in black.