Engrailed 2 触发了多个酸化诱导的信号通路的激活,无论是依赖转录的方式还是依赖转录的方式
Yong Cao1, Jie Jiang2, Xueqin Song1
1Experimental Medicine Center, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China; Luzhou Key Laboratory of Molecular Cancer, Luzhou, 646000, Sichuan, China.
Biochemical and biophysical research communications
|September 22, 2023
概括
嵌2 (EN2) 蛋白除了其转录因子作用外,还激活癌症信号通路. 阻断这些通路,包括NF-κB和AKT,显示了食道状细胞癌 (ESCC) 的治疗前景.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 信号传导传导是指信号的传导.
背景情况:
- 含有家庭主体 (HD) 的蛋白质,如Engrailed 2 (EN2),是已知的转录因子.
- 在各种癌症中,EN2的表达很高,但其精确的生物功能仍然不清楚.
- 了解EN2的机制对于开发有针对性的癌症疗法至关重要.
研究的目的:
- 阐明Engrailed 2 (EN2) 的转录独立功能.
- 为了识别EN2.2规范的信号通路.
- 探索针对癌症EN2的治疗策略,特别是食道状细胞癌 (ESCC).
主要方法:
- 蛋白质组分析,以在EN2表达上识别蛋白质酸化位的变化.
- 免疫沉质谱 (IP-MS) 用于检测蛋白相互作用.
- 验证EN2与PP2A-B55α复合物的相互作用,并评估其酸酶活性.
- 药理上抑制EN2-激活的NF-κB和AKT信号通路.
主要成果:
- EN2表现出转录独立的功能,通过酸化级联激活多个信号通路.
- EN2与许多参与酸化信号的蛋白质相互作用,包括B55α,抑制PP2A-B55α酸酶活性.
- 同时抑制EN2-激活的NF-κB和AKT通路显示出协同效应.
结论:
- 在癌症进展中,EN2具有重要的转录独立作用.
- EN2与PP2A-B55α的相互作用以及随后的途径激活有助于恶性瘤.
- 针对EN2介导的信号通路为ESCC提供了一个潜在的治疗策略.
相关概念视频
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
Interactions Between Signaling Pathways
6.3K
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...
6.3K
MAPK Signaling Cascades
5.6K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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
Intracellular Signaling Cascades
47.0K
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
47.0K
Amplifying Signals via Second Messengers
7.0K
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
7.0K


