TY - JOUR
T1 - Structural activation of Mad2 in the mitotic spindle checkpoint
T2 - The two-state Mad2 model versus the Mad2 template model
AU - Yu, Hongtao
PY - 2006/4/24
Y1 - 2006/4/24
N2 - The inheritance of a normal assortment of chromosomes during each cell division relies on a cell-cycle surveillance system called the mitotic spindle checkpoint. The existence of sister chromatids that do not achieve proper bipolar attachment to the mitotic spindle in a cell activates this checkpoint, which inhibits the ubiquitin ligase activity of the anaphase-promoting complex or cyclosome (APC/C) and delays the onset of anaphase. The mitotic arrest deficiency 2 (Mad2) spindle checkpoint protein inhibits APC/C through binding to its mitotic-specific activator, Cdc20. Binding of Mad2 to Cdc20 involves a large conformational change of Mad2 and requires the Mad1-Mad2 interaction in vivo. Two related but distinct models of Mad1-assisted activation of Mad2, the "two-state Mad2" and the "Mad2 template" models, have been proposed. I review the recent structural, biochemical, and cell biological data on Mad2, discuss the differences between the two models, and propose experiments that test their key principles.
AB - The inheritance of a normal assortment of chromosomes during each cell division relies on a cell-cycle surveillance system called the mitotic spindle checkpoint. The existence of sister chromatids that do not achieve proper bipolar attachment to the mitotic spindle in a cell activates this checkpoint, which inhibits the ubiquitin ligase activity of the anaphase-promoting complex or cyclosome (APC/C) and delays the onset of anaphase. The mitotic arrest deficiency 2 (Mad2) spindle checkpoint protein inhibits APC/C through binding to its mitotic-specific activator, Cdc20. Binding of Mad2 to Cdc20 involves a large conformational change of Mad2 and requires the Mad1-Mad2 interaction in vivo. Two related but distinct models of Mad1-assisted activation of Mad2, the "two-state Mad2" and the "Mad2 template" models, have been proposed. I review the recent structural, biochemical, and cell biological data on Mad2, discuss the differences between the two models, and propose experiments that test their key principles.
UR - http://www.scopus.com/inward/record.url?scp=33646092999&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646092999&partnerID=8YFLogxK
U2 - 10.1083/jcb.200601172
DO - 10.1083/jcb.200601172
M3 - Short survey
C2 - 16636141
AN - SCOPUS:33646092999
SN - 0021-9525
VL - 173
SP - 153
EP - 157
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 2
ER -