赛尔德通过阻断Bcl-3依赖的NF-kappaB信号传递来抑制瘤细胞的增殖
Ramin Massoumi1, Katarzyna Chmielarska, Katharina Hennecke
1Department of Molecular Medicine, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
Cell
|May 23, 2006
概括
CYLD基因二基因酶通过控制不同的NF-kappaB通路来调节皮肤瘤的生长. 失去CYLD会通过影响细胞增殖增加对化学诱导皮肤瘤的易感性.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 皮肤病学 皮肤病学
背景情况:
- CYLD基因的突变与毛囊皮细胞瘤有关.
- CYLD基因编码了一种参与调节细胞信号通路的二维基因酶.
- 在TRAF2上,CYLD二基因酶的活性准了素63结合的基因链,抑制了p65/p50核因子-kappaB (NF-kappaB) 的激活.
研究的目的:
- 研究CYLD基因在化学诱导的皮肤瘤发生中的作用.
- 阐明在角质细胞中由CYLD调节的特定NF-kappaB通路.
- 了解CYLD无活化如何促进皮肤瘤的发展和扩散.
主要方法:
- 使用Cyld淘汰赛 (Cyld-/-) 鼠标来评估对化学诱导皮肤瘤的敏感性.
- 用12-O-tetradecanoylphorbol-13乙酸 (TPA) 或紫外线治疗的分析Cyld-/-瘤和角质细胞,用于超增殖和环素D1水平.
- 研究了CYLD与Bcl-3和NF-kappaB组件 (p50,p52) 相关的核转移和脱活动.
主要成果:
- 缺乏Cyld (Cyld-/-) 的小鼠对化学诱导的皮肤瘤具有很高的敏感性.
- 循环-/- 瘤和经过治疗的角质细胞显示过度增殖和循环D1水平升高.
- CYLD无活化导致Bcl-3相关NF-kappaB p50和p52的核活性增加,导致扩散,而不是影响p65/p50的作用.
结论:
- 基于外部信号,CYLD对不同的NF-kappaB通路进行负调节.
- 由于CYLD对TRAF2的非激活会影响生存和炎症.
- 由CYLD抑制Bcl-3可以控制细胞增殖和瘤生长,这突显了CYLD在预防皮肤瘤发生方面的关键作用.
更多相关视频
相关概念视频
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...
Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The Intrinsic Apoptotic Pathway
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...


