阿里碳化合物核转位器改变了CD30介导的NF-kappaB依赖转录
Casey W Wright1, Colin S Duckett
1Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Science (New York, N.Y.)
|January 10, 2009
概括
基碳化合物受体核转位器 (ARNT) 与淋巴瘤中的CD30信号相互作用. 缺少ARNT会改变转录因子NF-kappaB的活性,影响癌细胞中的基因表达.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- CD30是一种受体,在像霍奇金淋巴瘤和形大细胞淋巴瘤 (ALCL) 等淋巴状癌症中受到上调.
- 了解CD30信号传递机制对于开发向癌症疗法至关重要.
研究的目的:
- 阐明 CD30 信号的基础分子机制.
- 确定与CD30相互作用的蛋白质及其在调节下游通路中的作用.
主要方法:
- 使用一种亲和性净化策略来识别CD30相互作用蛋白.
- 研究了基碳化合物受体核转位器 (ARNT) 对ALCL细胞中核因子kappaB (NF-kappaB) 活性的影响.
主要成果:
- 确定ARNT是一种与CD30相互作用的蛋白质,可调节NF-kappaB.的RelB亚单元.
- 缺少ARNT的ALCL细胞显示RelB招募受损,但增强了对NF-kappaB促进体的RelA招募.
- 这导致了RNA缺乏细胞中NF-kappaB响应基因的增强表达.
结论:
- ARNT在CD30介导的信号通路中发挥作用.
- 在CD30诱导的反应中,ARNT与RelB作为负反循环的一部分.
- 这些发现提供了关于淋巴细胞恶性瘤中NF-kappaB的调节的见解.
相关概念视频
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:31Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
02:26NF-kB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...