酸果酸酶1糖化调节细胞生长和新陈代谢
Wen Yi1, Peter M Clark, Daniel E Mason
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
概括
癌细胞利用与O相关的β-N-乙糖胺 (O-GlcNAcylation) 来改变葡萄糖代谢以促进生长. 抑制这种对酸果酸酶1 (PFK1) 的修饰会阻碍癌细胞的增殖和瘤的形成.
科学领域:
- 生物化学 生物化学
- 癌症生物学 癌症生物学
- 代谢调节 代谢调节 代谢调节 代谢调节
背景情况:
- 癌细胞需要显著的代谢适应才能快速生长.
- 翻译后的修改,如O-链 β-N-乙糖胺 (O-GlcNAcylation),在调节细胞过程中起着至关重要的作用.
- 葡萄糖代谢在癌症中经常发生改变,以支持扩散.
研究的目的:
- 研究O-GlcNAcylation在低氧条件下调节癌细胞代谢中的作用.
- 为了确定参与代谢重编程的O-GlcNAcylation的特定蛋白质标.
- 评估向O-GlcNAcylation在癌症中的治疗潜力.
主要方法:
- 在癌细胞中分析O-GlcNAcylation动态.
- 在血清529中对酸果酶1 (PFK1) 的特定位点的修改.
- 通过代谢途径评估葡萄糖流量,包括酸途径.
- 在体外增殖试验和体内瘤形成研究.
主要成果:
- 低氧诱导的O-GlcNAcylation在PFK1.1的血清529的
- PFK1的O-GlcNAcylation抑制了它的酶活性.
- 这种修改将葡萄糖代谢重定向到酸途径,促进癌细胞生长.
- 阻断PFK1糖化减少了癌细胞的增殖和瘤的生长.
结论:
- PFK1的O-GlcNAcylation是一种新的调节癌细胞代谢的机制.
- 向PFK1糖基化提供了癌症治疗的潜在治疗策略.
- 了解癌症中的代谢适应对于开发有效干预措施至关重要.
相关概念视频
What is Glycolysis?
Overview
Cells make energy by breaking down macromolecules. Cellular respiration is the biochemical process that converts "food energy" (from the chemical bonds of macromolecules) into chemical energy in the form of adenosine triphosphate (ATP). The first step of this tightly regulated and intricate process is glycolysis. The word glycolysis originates from the Latin glyco (sugar) and lysis (breakdown). Glycolysis serves two main intracellular functions: generating ATP and generating...
Cells make energy by breaking down macromolecules. Cellular respiration is the biochemical process that converts "food energy" (from the chemical bonds of macromolecules) into chemical energy in the form of adenosine triphosphate (ATP). The first step of this tightly regulated and intricate process is glycolysis. The word glycolysis originates from the Latin glyco (sugar) and lysis (breakdown). Glycolysis serves two main intracellular functions: generating ATP and generating...
PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Glycolysis: Preparatory Phase
In cellular metabolism (the complete breakdown of glucose to extract energy), glycolysis is the first step. Glycolysis takes place in the cytoplasm of both prokaryotic and eukaryotic cells. Glucose enters heterotrophic cells in two ways. One method is through secondary active transport, where the transport takes place against the glucose concentration gradient. The other mechanism uses a group of integral proteins called GLUT proteins, also known as glucose transporter proteins. These...
Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...

