DBC1是SIRT1的负调节者
Ja-Eun Kim1, Junjie Chen, Zhenkun Lou
1Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nature
|February 1, 2008
概括
Deleted in Breast Cancer-1 (DBC1) 直接抑制了与衰老和癌症相关的蛋白质SIRT1的活性. 减少DBC1可以增强SIRT1.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 依赖NAD的蛋白质脱乙酶Sir2 (静音信息调节器2) 对于调节生物体的寿命至关重要.
- 酵母Sir2的哺乳动物同类物SIRT1在各种细胞功能和潜在的瘤发生中发挥作用.
- 虽然SIRT1的细胞作用得到了充分的研究,但其活动调节仍然不太了解.
研究的目的:
- 研究SIRT1活动的调控机制.
- 为了识别与SIRT1功能相互作用和调节的蛋白质.
- 探索SIRT1调节对衰老和癌症的影响.
主要方法:
- 同免疫沉试验检测DBC1和SIRT1.1之间的蛋白质复合体形成.
- 在体外和体内测试以测量SIRT1脱乙酶活性.
- 基因沉默技术 (例如,siRNA) 来降低DBC1表达的调节.
- 在基因毒性压力后诱导亡的分析.
主要成果:
- 被删除的乳腺癌-1 (DBC1) 与SIRT1.1形成了一个稳定的复合体.
- 在体外和体内,DBC1直接与SIRT1相互作用并抑制SIRT1的活动.
- 降低DBC1表达的调节增强了SIRT1介导的抑制因基因毒性压力引起的亡.
结论:
- DBC1作为SIRT1活动的直接负调节剂.
- 这些发现为SIRT1.1调节提供了新的见解.
- DBC1和SIRT1之间的相互作用对理解衰老和癌症背后的分子机制具有重大意义.
相关概念视频
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
02:39Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
02:39Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
02:34Inhibition of CDK Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...