通过DBC1对脱乙酶SIRT1进行负调节
Wenhui Zhao1, Jan-Philipp Kruse, Yi Tang
1Institute for Cancer Genetics, and Department of Pathology College of Physicians and Surgeons, Columbia University, 1130 St Nicholas Avenue, New York, New York 10032, USA.
Nature
|February 1, 2008
概括
乳腺癌中被删除的1 (DBC1) 抑制SIRT1脱乙酶的活性. DBC1的枯竭会增强SIRT1的作用.
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:
- SIRT1,一种依赖NAD的脱乙酶,调节压力反应,新陈代谢和衰老.
- SIRT1脱乙基化瘤抑制剂p53,促进细胞存活.
- 在体内SIRT1活动的调节仍然不太清楚.
研究的目的:
- 为了研究SIRT1活动的体内调节.
- 为了确定SIRT1.1.的本源抑制剂.
- 阐明DBC1在SIRT1介导的p53调节中的作用.
主要方法:
- 对于DBC1枯竭的RNA干扰 (RNAi).
- 对p53乙化和亡的分析.
- 测试SIRT1活动.
主要成果:
- 在人类细胞中,DBC1充当SIRT1的本源抑制剂.
- 通过DBC1介导的SIRT1抑制会增加p53的乙化和功能.
- DBC1 枯竭刺激了 SIRT1 的活性,导致p53 脱乙和抑制了亡.
结论:
- DBC1 特别抑制了 SIRT1 脱乙酶的活性.
- 通过抑制SIRT1.1,DBC1促进了p53介导的亡.
- DBC1是SIRT1功能的关键调节者,在细胞过程中发挥作用,如细胞亡.
相关概念视频
Negative 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.
Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
Inhibition 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...
Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
Inhibition 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...


