The APC/C maintains the spindle assembly checkpoint by targeting Cdc20 for destruction

TY - JOUR

T1 - The APC/C maintains the spindle assembly checkpoint by targeting Cdc20 for destruction

AU - Nilsson, Jakob

AU - Yekezare, Mona

AU - Minshull, Jeremy

AU - Pines, Jonathon

N1 - Keywords: Amino Acid Motifs; Calcium-Binding Proteins; Cell Cycle Proteins; Chromatography, Gel; Hela Cells; Humans; Lysine; Mitotic Spindle Apparatus; Mutant Proteins; Protein Binding; Protein Processing, Post-Translational; Protein-Serine-Threonine Kinases; Repressor Proteins; Ubiquitin-Protein Ligase Complexes; Ubiquitination

PY - 2008

Y1 - 2008

N2 - The spindle assembly checkpoint (SAC) is required to block sister chromatid separation until all chromosomes are properly attached to the mitotic apparatus. The SAC prevents cells from entering anaphase by inhibiting the ubiquitylation of cyclin B1 and securin by the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase. The target of the SAC is the essential APC/C activator Cdc20. It is unclear how the SAC inactivates Cdc20 but most current models suggest that Cdc20 forms a stable complex with the Mad2 checkpoint protein. Here we show that most Cdc20 is not in a complex with Mad2; instead Mad2 is required for Cdc20 to form a complex with another checkpoint protein, BubR1. We further show that during the SAC, the APC/C ubiquitylates Cdc20 to target it for degradation. Thus, ubiquitylation of human Cdc20 is not required to release it from the checkpoint complex, but to degrade it to maintain mitotic arrest.

AB - The spindle assembly checkpoint (SAC) is required to block sister chromatid separation until all chromosomes are properly attached to the mitotic apparatus. The SAC prevents cells from entering anaphase by inhibiting the ubiquitylation of cyclin B1 and securin by the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase. The target of the SAC is the essential APC/C activator Cdc20. It is unclear how the SAC inactivates Cdc20 but most current models suggest that Cdc20 forms a stable complex with the Mad2 checkpoint protein. Here we show that most Cdc20 is not in a complex with Mad2; instead Mad2 is required for Cdc20 to form a complex with another checkpoint protein, BubR1. We further show that during the SAC, the APC/C ubiquitylates Cdc20 to target it for degradation. Thus, ubiquitylation of human Cdc20 is not required to release it from the checkpoint complex, but to degrade it to maintain mitotic arrest.

U2 - 10.1038/ncb1799

DO - 10.1038/ncb1799

M3 - Journal article

C2 - 18997788

SN - 1465-7392

VL - 10

SP - 1411

EP - 1420

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 12

ER -