通过偏酶调节NF-kappaB依赖性淋巴细胞的激活和发育
Astrid A Ruefli-Brasse1, Dorothy M French, Vishva M Dixit
1Molecular Oncology Department, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
概括
帕拉卡斯巴酶 (MALT1) 对于通过NF-kappaB通路激活T和B淋巴细胞至关重要. 它的缺乏会损害免疫反应,突出其在Bcl10下游在免疫细胞发育和功能中的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 帕拉卡斯帕斯 (MALT1) 是一种类似卡斯帕斯的蛋白质.
- 它与Bcl10结合,并参与NF-kappaB激活的CARMA1-Bcl10通路.
- 帕拉卡斯帕斯在淋巴细胞激活中的确切作用尚不清楚.
研究的目的:
- 为了研究对抗原受体诱导的免疫反应中帕拉卡斯帕斯的功能.
- 确定帕拉卡斯帕斯在T和B淋巴细胞激活,细胞因子产生和增殖中的作用.
- 为了阐明帕拉卡斯帕斯在NF-kappaB信号级联中的位置.
主要方法:
- 来自缺陷帕拉卡斯帕斯酶的小鼠初级T和B淋巴细胞的分析.
- 评估NF-kappaB激活,细胞因子产生和细胞增殖.
- 调查Bcl10下游的信号通路.
主要成果:
- 甲酶缺乏的淋巴细胞显示了抗原受体诱导的NF-kappaB激活的缺陷.
- 在没有帕拉卡斯帕斯的情况下,细胞因子的产生和淋巴细胞的增殖受损.
- 发现帕拉卡斯帕斯在信号通路中作用于Bcl10的下游.
结论:
- 帕拉卡斯巴酶 (MALT1) 在T和B淋巴细胞中对NF-kappaB激活至关重要.
- 它在正常的B细胞发育中起着至关重要的作用.
- 帕拉卡斯帕斯桥梁 Bcl10 和 IkappaB 激酶复合体激活,提供免疫信号的缺失环节.
更多相关视频
相关概念视频
Co-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...
Regulation 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...
NF-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...
TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
NF-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...


