通过抑制一种美林酸酶,通过CPI-17进行瘤原生转化
Hongchuan Jin1, Tobias Sperka, Peter Herrlich
1Leibniz Institute of Age Research-Fritz-Lipmann-Institute, Beutenbergstrasse 11, 07745 Jena, Germany.
Nature
|August 4, 2006
概括
肌酸酸酶 (MYPT-1-PP1delta) 通过去酸化来激活瘤抑制剂默林. 它的抑制剂CPI-17通过破坏这种美林通路来促进癌症,突出显示了一种新的瘤抑制剂级联.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 默林 (神经纤维素瘤类型2基因NF2) 是一种调节细胞增殖的瘤抑制剂.
- 默林激活需要在血清518 (S518) 处进行脱化,但不清楚负责的酸酶.
研究的目的:
- 为了识别激活梅林瘤抑制功能的酸酶.
- 调查这种酸酶及其抑制剂在癌症中的作用.
主要方法:
- 酶识别试验. 酶识别试验.
- 使用默林突变体和CPI-17抑制剂进行细胞测试.
- 在人类瘤细胞系中分析CPI-17水平.
主要成果:
- 肌酸酸酶 (MYPT-1-PP1delta) 被确定为激活美林的酸酶.
- 特定于MYPT-1-PP1delta的抑制剂CPI-17会导致美林酸化,Ras激活和细胞转化.
- 降低CPI-17的调节逆转了这些致癌效应,证实了默林是关键基质.
结论:
- MYPT-1-PP1delta和merlin形成了一个新的瘤抑制剂级联.
- 这种级联可以被NF2突变或CPI-17水平的增加所破坏,从而导致瘤发生.
相关概念视频
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...
Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
Interactions Between Signaling Pathways
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...
PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Somatic cells are...
