The HECT E3 ligase Smurf2 is required for Mad2-dependent spindle assembly checkpoint.
The HECT E3 ligase Smurf2 is required for Mad2-dependent spindle assembly checkpoint.
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HECT E3连接酶Smurf2是MAD2依赖性纺锤体组件检查点所需的。
DOI：
10.1083/jcb.200801049
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发表时间：
2008-10-20
影响因子：
7.8
通讯作者：
Kiyokawa, Hiroaki
中科院分区：
文献类型：
--
作者：
Osmundson, Evan C.;Ray, Dipankar;Moore, Finola E.;Gao, Qingshen;Thomsen, Gerald H.;Kiyokawa, Hiroaki
Cdc 20激活后期促进复合物/细胞周期体（APC/C）对于中期-后期转换是至关重要的。APC/C-Cdc 20是分裂后期启动时securin和cyclin B的多聚泛素化和降解所必需的。纺锤体组装检查点延迟APC/C-Cdc 20激活，直到所有动粒附着到有丝分裂纺锤体。在这项研究中，我们证明，HECT（同源的E6-AP羧基末端）泛素连接酶，Smurf 2，是必需的纺锤体检查点。Smurf 2定位于中心体、有丝分裂中体和着丝粒。Smurf 2缺失或无催化活性的Smurf 2的表达导致染色体错位和滞后，过早的后期开始和有缺陷的胞质分裂。Smurf 2失活防止诺考达唑处理的细胞积累细胞周期蛋白B和securin和前中期停滞。Smurf 2缺失细胞中Cdc 20的沉默恢复了细胞周期蛋白B和securin的有丝分裂积累。Smurf 2缺失导致Mad 2的多聚泛素化和降解增强，Mad 2是一种关键的检查点效应物。Mad 2在Smurf 2缺失的细胞中错误定位，表明Smurf 2调节Mad 2的定位和稳定性。这些数据表明Smurf 2是一种新的有丝分裂调节因子。
Activation of the anaphase-promoting complex/cyclosome (APC/C) by Cdc20 is critical for the metaphase–anaphase transition. APC/C-Cdc20 is required for polyubiquitination and degradation of securin and cyclin B at anaphase onset. The spindle assembly checkpoint delays APC/C-Cdc20 activation until all kinetochores attach to mitotic spindles. In this study, we demonstrate that a HECT (homologous to the E6-AP carboxyl terminus) ubiquitin ligase, Smurf2, is required for the spindle checkpoint. Smurf2 localizes to the centrosome, mitotic midbody, and centromeres. Smurf2 depletion or the expression of a catalytically inactive Smurf2 results in misaligned and lagging chromosomes, premature anaphase onset, and defective cytokinesis. Smurf2 inactivation prevents nocodazole-treated cells from accumulating cyclin B and securin and prometaphase arrest. The silencing of Cdc20 in Smurf2-depleted cells restores mitotic accumulation of cyclin B and securin. Smurf2 depletion results in enhanced polyubiquitination and degradation of Mad2, a critical checkpoint effector. Mad2 is mislocalized in Smurf2-depleted cells, suggesting that Smurf2 regulates the localization and stability of Mad2. These data indicate that Smurf2 is a novel mitotic regulator.
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影响因子：
4.8
作者：
Jin, YH;Jeon, EJ;Bae, SC
通讯作者：
Bae, SC
影响因子：
16
作者：
Dong, CM;Li, ZR;Goldschmidt-Clermont, PJ
通讯作者：
Goldschmidt-Clermont, PJ
DOI：
10.1098/rstb.1999.0502
发表时间：
1999-09-29
期刊：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
Fang, GW;Yu, HT;Kirschner, MW
通讯作者：
Kirschner, MW
影响因子：
11.8
作者：
Han, Gangwen;Li, Allen G.;Wang, Xiao-Jing
通讯作者：
Wang, Xiao-Jing
影响因子：
16
作者：
Kavsak, P;Rasmussen, RK;Wrana, JL
通讯作者：
Wrana, JL