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相关概念视频

The Ras Gene02:38

The Ras Gene

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The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
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Mutations01:35

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Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
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Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
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在 LZTR1 中的突变通过调节 RAS 无处不在导致人类疾病

M Steklov1,2, S Pandolfi1,2, M F Baietti1,2

  • 1VIB-KU Leuven Center for Cancer Biology, VIB, 3000 Leuven, Belgium.

Science (New York, N.Y.)
|November 17, 2018
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概括

氨酸拉皮式转录调节器1 (LZTR1) 蛋白通过介导无处不在来调节RAS信号. 失去LZTR1功能会导致诺南综合征,并影响施万细胞的增殖,解释其在人类疾病中的作用.

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科学领域:

  • 分子生物学
  • 遗传学
  • 细胞生物学

背景情况:

  • 氨酸拉链状转录调节剂1 (LZTR1) 蛋白质是库林3 (CUL3) 泛酶复合体的适配剂.
  • 目前尚不清楚LZTR1的确切作用机制以及它对人类疾病的作用.

研究的目的:

  • 阐明LZTR1功能的分子机制.
  • 调查LZTR1,RAS信号传递和像努南综合症这样的人类疾病之间的联系.

主要方法:

  • 从哺乳动物细胞中捕获LZTR1复合体.
  • 用于确定蛋白质无处不在的变化.
  • 与疾病相关的LZTR1突变的分析.

主要成果:

  • LZTR1 作为 CUL3 无酸酶复合物的适配剂,向关三酸酶 RAS.
  • 在lysine-170中通过LZTR1介导的RAS泛化通过减少膜关联来抑制RAS信号传递.
  • 在小鼠中Lztr1的丧失重现了诺南综合征的表型,并影响了施万细胞的行为.
  • 已识别的与疾病相关的LZTR1突变会影响复合体形成或RAS相互作用.

结论:

  • 通过LZTR1介导的RAS无处不在是一种关键的调节机制.
  • 这种途径的失调解释了LZTR1参与人类疾病,包括努南综合征.