对Skp2功能的乙化依赖调节
Hiroyuki Inuzuka1, Daming Gao, Lydia W S Finley
1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Cell
|July 10, 2012
概括
由p300和SIRT3调节的异常Skp2乙化,增加了Skp2的稳定性,并促进了癌细胞的迁移和增殖. 这种乙化机制控制了Skp2.
科学领域:
- 分子瘤学分子瘤学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
背景情况:
- 异常的Skp2信号传递是瘤发生的关键驱动因素.
- 细胞质Skp2与侵袭性乳腺癌和前列腺癌相关,但机制尚不清楚.
研究的目的:
- 要阐明Skp2.的乙化依赖调节.
- 研究细胞质Skp2在癌症进展中的作用.
主要方法:
- 研究了Skp2通过p300的乙化和SIRT3.3的脱乙化.
- 通过Cdh1通路分析了Skp2的稳定性和蛋白质分解.
- 利用乙化模仿突变体来评估细胞增殖和瘤发生.
- 检查了Skp2局部化,E-cadherin无处不在和细胞迁移.
主要成果:
- 在K68和K71的位置上,Skp2由p300进行乙化,并被SIRT3.3对抗.
- 通过SIRT3的不激活,增加了Skp2的乙化,通过抑制Cdh1介导的降解来增强稳定性.
- 乙化模仿性Skp2突变体显示增加的增殖和瘤发生.
- 在核定位信号 (NLS) 中的Skp2乙化促进了细胞质保留.
- 细胞质Skp2通过促进E-cadherin的无化和降解来增强迁移.
结论:
- 确定了一种新的乙化依赖的Skp2瘤功能调节机制.
- 证明细胞质Skp2通过E-cadherin调节控制细胞迁移.
- 提供了对Skp2在侵袭性癌症中的作用的机制性见解.
相关概念视频
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