检查点诱导的shugoshin-MAD2分离酶的securin独立调节
Susanne Hellmuth1, Laura Gómez-H2, Alberto M Pendás2
1Chair of Genetics, University of Bayreuth, Bayreuth, Germany.
Nature
|April 24, 2020
概括
舒戈辛2 (SGO2) 作为一种新型分离酶抑制剂,补充了securin
科学领域:
- 细胞生物学
- 分子生物学
- 遗传学
背景情况:
- 在真核细胞中,姐妹染色体的分离是由螺旋组合检查点 (SAC) 和蛋白酶分离酶调节的.
- 塞库林通常抑制分离酶,其通过APC/ C (酶促进复合体) 的降解激活分离酶.
- 在没有securin的情况下,分离酶的调节仍然不清楚.
研究的目的:
- 研究人体舒戈辛2 (SGO2) 在体细胞中调节分离酶活性中的作用.
- 阐明SGO2抑制分离酶的机制以及这种抑制是如何调节的.
- 了解SGO2,securin和染色体分离中的螺旋组合检查点之间的相互作用.
主要方法:
- 在螺旋组装检查点的背景下研究了SGO2和MAD2之间的相互作用.
- 使用securin-knockout细胞研究SGO2的分离酶调节.
- 进行了体外测定,以分析SGO2-MAD2对分离酶的抑制机制和该复合物的调节.
主要成果:
- 在与SAC激活的MAD2结合后,SGO2作为分离酶抑制剂起作用,形成SGO2- MAD2复合体.
- 该SGO2-MAD2复合物有效地隔离分离酶,在功能上取代securin-knockout细胞.
- 失去了securin和SGO2导致过早的凝聚素分裂和细胞毒性,表明它们的合作作用.
- 通过类似于securin的伪基质序列,SGO2通过阻断其活性部位来抑制分离酶.
- 从SGO2-MAD2中通过APC/C依赖的无处不在和TRIP13和p31的作用释放分离酶.
结论:
- 鉴定了SGO2作为分离酶抑制剂在线粒分裂体细胞中的新型作用.
- 发现了一种由组合检查点监督的独立于securin的分离调节机制.
- SGO2-MAD2复合物为控制分离酶活性提供了至关重要的保护措施,特别是当securin缺失时.
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