Scientists Unveil New Defense Mechanism of Cancer

Scientists from University of Copenhagen have identified a new molecular mechanism of cell division which could be very important in the process of canceration. This finding was published in Nature Communication.

Accurate chromosome segregation during mitosis is ensured by the spindle assembly checkpoint(SAC), which is a conserved mechanism requiring the Aurora B, Mad1, Mad2, Mps1, Bub1, BubR1(Mad3 in yeast) and Bub3 proteins. Improperly attached kinetochores activate the SAC and by an unknown mechanism catalyse the binding two checkpoint proteins, Mad 2 and BubR1, to Cdc20 forming the mitotic checkpoint complex (MCC).

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In this study, researchers address the functional role of Cdc20 kinetochore localization in the SAC, they delineate the molecular details of its interaction with kinetochores. The research team finds that BubR1 recruits the bulk of Cdc20 to kinetochores through its internal Cdc20 binding domain (IC20BD). They also show that preventing Cdc20 kinetochore localization by removal of the IC20BD has a limited effect on the SAC because the IC20BD is also required for efficient SAC silencing.

Thus, scientists uncover an unexpected dual function of the second Cdc20 binding site in BubR1 in promoting both efficient SAC signaling and SAC silencing. The researchers hope to develop new anti-cancer therapy on the basis of this new finding and predict reactions of different drug therapies.

Reference:

Lischetti T, Zhang G, Sedgwick G G, et al. The internal Cdc20 binding site in BubR1 facilitates both spindle assembly checkpoint signalling and silencing[J]. Nature Communications, 2014, 5.

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