通过PLK1介导的PHGDH酸化在晚期前列腺癌中重新编程了血清代谢
Xiongjian Rao1,2, Derek B Allison2, Robert M Flight2
1Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA.
bioRxiv : the preprint server for biology
|June 6, 2025
概括
波罗样酶1 (PLK1) 通过改变血清酶代谢来驱动癌症的生长. 它酸化PHGDH,减少血清素合成,增加对脂质生产的外部血清素的依赖,提供新的治疗点.
科学领域:
- 生物化学 生物化学
- 癌症生物学 癌症生物学
- 代谢途径 代谢途径
背景情况:
- 癌细胞重新编程新陈代谢,以满足高能量和生物合成需求.
- 转变的癌细胞通常依赖外源血清来生长,但调节机制尚不清楚.
研究的目的:
- 调查Polo样酶1 (PLK1) 在调节癌症中血清和脂质代谢中的作用.
- 阐明PLK1影响血清蛋白合成途径 (SSP) 的机制.
主要方法:
- 研究了PLK1和糖酸脱酶 (PHGDH) 之间的相互作用.
- 分析了PLK1酸化对PHGDH活性和蛋白质水平的影响.
- 研究了SSP下调对血清素摄取和脂质生物合成的影响.
主要成果:
- 在特定的部位 (S512,S513,S517) 化PHGDH,降低其活性和蛋白质水平.
- 对SSP的下调会增加癌细胞依赖ASCT2的外源血清吸收.
- 增加的血清素吸收促进了脂质生物合成,包括瘤生长所必需的脂质.
结论:
- 通过PLK1介导的PHGDH调节代表了一种新的机制,驱动癌症中的代谢依赖.
- 准SSP,血清吸收或脂质生物合成途径可能在PLK1-高的癌症中有效.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
4.0K
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...
4.0K
Protein Kinases and Phosphatases
13.5K
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...
13.5K
Phosphorylation
51.3K
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...
51.3K
mTOR Signaling and Cancer Progression
3.9K
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...
3.9K
Amplifying Signals via Enzymatic Cascade
9.9K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
9.9K
Interactions Between Signaling Pathways
6.6K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.6K


