TRIM16调解了DAB2的K63连接的泛化,以促进血管化
Zirong Lan1,2,3, Qingchun Liang4, Li Li1,5
1Department of Cardiology, Laboratory of Heart Center, Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China (Z.L., F.L., A.C., Y.Y., L.F., Z.Z., X.Z., J.Y.).
Circulation research
|June 27, 2025
概括
E3 泛基因酶TRIM16通过向DAB2进行泛基因化,加剧血管化,影响整体蛋白β1内细胞分裂和FAK-STAT3信号传递. 这种TRIM16-DAB2通路为治疗血管化提供了潜在的治疗标.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 腎臟病學 (nephrology) 是一種醫學.
背景情况:
- 血管化在慢性病 (CKD) 中很常见.
- 蛋白质无化在血管化中起着重要作用.
- 在这个过程中,E3泛素酶的具体作用尚不清楚.
研究的目的:
- 调查E3泛酸酶TRIM16在血管化中的作用.
- 阐明TRIM16调节血管化的分子机制.
主要方法:
- 在细胞和动物模型中诱导血管化 (CKD小鼠/大鼠,维生素D3过载的小鼠).
- 使用基因操纵 (siRNA,淘汰赛小鼠) 来改变TRIM16和DAB2水平.
- 采用免疫沉质谱和无处不在的测试来识别和描述蛋白质相互作用和修饰.
主要成果:
- 在各种模型中,TRIM16表达在血管化过程中增加,并加剧了化.
- TRIM16与DAB2直接相互作用,催化其与K63结合的无化.
- 由TRIM16诱导的DAB2无化促进了整体蛋白β1内和FAK-STAT3信号激活,导致VSMC化.
结论:
- 通过使DAB2无处不在,TRIM16促进了血管化,从而导致整合素β1内分细胞和FAK-STAT3通路的激活.
- TRIM16-DAB2轴是一个新的治疗点,用于控制CKD中的血管化.
相关概念视频
Covalently Linked Protein Regulators
7.4K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
7.4K
Receptor Downregulation in MVBs
2.2K
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...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.2K
Regulation of Angiogenesis and Blood Supply
2.7K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.7K


