碳氧胺酶A4通过与AKT信号通路形成正反循环来负面调节HGS-ETR1/2-诱导的热
Luoling Wang1, Rilin Deng1, Shuishun Chen1
1Institute of Pathogen Biology and Immunology, College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha, 410082, China.
Cell death & disease
|December 4, 2023
概括
HGS-ETR1/2抗体触发肝细胞癌细胞死通过烧灭. 这项研究揭示了一种新的调节途径,该途径涉及CPA4和AKT信号在这个过程中.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 热症是一种炎症性细胞死亡途径,其机制尚未完全理解.
- HGS-ETR1/2是一种向DR4/5的单克隆抗体,已知可以通过死亡受体信号诱导亡.
研究的目的:
- 研究肝细胞癌中HGS-ETR1/2-诱导细胞死亡的机制.
- 阐明CPA4和AKT信号在HGS-ETR1/2-介导的热中所起的作用.
主要方法:
- 形态观察 形态观察
- 光二重染色法 光二重染色法
- 在LDH释放测试中测试LDH释放测试.
- 免疫块检测检测 免疫块检测检测
主要成果:
- 在肝细胞癌细胞中,HGS-ETR1/2诱导了GSDME介导的烧.
- 抑制AKT信号传递和CPA4沉默会促进热;CPA4过度表达会抑制它.
- 在CPA4和AKT酸化之间存在一个积极的反循环,由PP2A介导并影响CPA4的表达.
结论:
- 在肝细胞癌中,HGS-ETR1/2通过一种涉及CPA4和AKT信号传递的新机制诱导热.
- 这一发现为开发新的癌症免疫疗法提供了基础.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.6K
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...
3.6K
Amplifying Signals via Enzymatic Cascade
8.5K
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...
8.5K
GPCRs Regulate Adenylyl Cylase Activity
5.6K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.6K
cAMP-dependent Protein Kinase Pathways
6.4K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.4K
Regulation of Angiogenesis and Blood Supply
2.6K
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...
2.6K
Allosteric Proteins-ATCase
5.8K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.8K


