确定一个调节细胞死细胞死亡途径的分子信号网络
Junichi Hitomi1, Dana E Christofferson, Aylwin Ng
1Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Cell
|December 27, 2008
概括
研究人员确定了432个调节细胞死亡途径 - - 亡的基因. 这项研究定义了控制亡和亡的信号网络,揭示了先天免疫的关键调节者.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 像FasL和TNFalpha这样的死亡受体激活剂会触发亡或亡.
- 亡是一种依赖于RIP1激酶的编程亡,发生在缺乏亡机制的细胞中.
研究的目的:
- 使用全基因组屏幕识别调节亡的基因.
- 阐明控制亡与亡之间的分支的信号网络.
主要方法:
- 全基因组的siRNA屏幕用于识别亡调节者.
- 在特定的生物系统中对基因表达丰富的分析.
- 鉴定参与亡和亡的基因.
主要成果:
- 鉴定出了一组432个调节亡的基因.
- 发现了32个基因,它们作用于下游或作为RIP1激酶的调节者.
- 7个基因被确定为亡和亡的共同调节者.
- 在免疫和神经系统中观察到基因表达丰富.
- 发现Bmf是Bcl-2家族成员,对于亡是必不可少的.
结论:
- 已经定义了一个全面的信号网络来调节亡.
- 这项研究阐明了控制死和死之间的切换的分子机制.
- 亡调节涉及与先天免疫相关的广泛网络.
相关概念视频
Overview of Cell Death
7.8K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
7.8K
The Extrinsic Apoptotic Pathway
6.2K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.2K
The Intrinsic Apoptotic Pathway
6.2K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K
Necrosis
5.3K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
5.3K
Cellular Injury IlI: Cellular Death
93
Cell death is the irreversible loss of cellular structure and function, representing the final stage of severe injury. It plays a key role in both normal physiology and disease.Types of Cell DeathThe two main types are necrosis and apoptosis, though others like necroptosis and pyroptosis also exist.Necrosis:Necrosis is an unregulated form of cell death caused by severe injury such as trauma, toxins, or ischemia. It is characterized by cell swelling, membrane loss, rupture, and leakage of...
93
Cellular Injury IV: Necrosis
97
Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...
97


