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在proline-hydroxylation-dependent方式中抑制Akt的激酶活性
Jianping Guo1, Abhishek A Chakraborty2, Pengda Liu1
1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Science (New York, N.Y.)
|August 27, 2016
在PubMed 上查看摘要
概括
低氧和与癌症相关的突变激活了Akt,这是促进瘤生长和治疗耐药性的关键蛋白质. 这发生在EglN1酶化Akt时,使pVHL能够抑制它.
科学领域:
- 生物化学
- 分子生物学
- 癌症学
背景情况:
- 氨酸-氨酸激酶Akt对于癌细胞的存活和增殖至关重要.
- 在低氧条件下,瘤细胞对治疗具有抗性.
研究的目的:
- 研究缺氧与癌症中的Akt活性之间的联系.
- 阐明调节Akt激活的分子机制以应对氧气水平.
主要方法:
- 用Prolyl-hydroxylation测试来确定EglN1对Akt的改变.
- 共同免疫沉以评估基化Akt与pVHL之间的相互作用.
- 在具有不同氧度或pVHL功能的细胞中分析Akt活性.
- 与癌症相关的Akt突变的识别和表征.
主要成果:
- 通过依赖氧气的方式通过EglN1进行prolyl-hydroxylation.
- 氧化Akt与pVHL结合,从而抑制Akt的活性.
- 氧气或pVHL功能丧失导致Akt激活,促进细胞存活和瘤形成.
- 鉴定出与癌症相关的Akt突变,这些突变阻止了化和pVHL结合,导致Akt过活化.
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