Functional interaction between BubR1 and securin in an anaphase-promoting complex/cyclosomeCdc20-independent manner.
Activation of the mitotic checkpoint requires the precise timing and spatial organization of mitotic regulatory events, and ensures accurate chromosome segregation. Mitotic checkpoint proteins such as BubR1 and Mad2 bind to Cdc20, and inhibit anaphase-promoting complex/cyclosome(Cdc20)-mediated securin degradation and the onset of anaphase. BubR1 mediates the proper attachment of microtubules to kinetochores, and links the regulation of chromosome-spindle attachment to mitotic checkpoint signaling. Therefore, disruption of BubR1 activity results in a loss of the checkpoint control, chromosome instability, and/or early onset of malignancy. In this study, we show that BubR1 directly interacts with securin in vitro and in vivo. In addition, the BubR1 interaction contributes to the stability of securin, and there is a significant positive correlation between BubR1 and securin expressions in human cancer. Importantly, BubR1 competes with Cdc20 for binding to securin, and thereby the interaction between BubR1 and securin is greatly increased by the depletion of Cdc20. Our findings may identify a novel regulation of BubR1 that can generate an additional anaphase-inhibitory signal through the Cdc20-independent interaction of BubR1 with securin.
Kim
Hyun-Soo
HS
Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi, Korea.
Jeon
Yoon-Kyung
YK
Ha
Geun-Hyoung
GH
Park
Hye-Young
HY
Kim
Yu-Jin
YJ
Shin
Hyun-Jin
HJ
Lee
Chang Geun
CG
Chung
Doo-Hyun
DH
Lee
Chang-Woo
CW
D064173:Anaphase-Promoting Complex-Cyclosome; D001667:Binding, Competitive; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D064249:Securin; D014162:Transfection; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; C577488:CDC20 protein, human; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases