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相关概念视频

Long-patch Base Excision Repair01:02

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Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
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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...
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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.
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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.
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MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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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...
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相关实验视频

Updated: May 5, 2026

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
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Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

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ARF-BP1/Mule是ARF瘤抑制剂的关键调解者.

Delin Chen1, Ning Kon, Muyang Li

  • 1Institute for Cancer Genetics, Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St. Nicholas Avenue, New York, New York 10032.

Cell
|July 2, 2005
PubMed
概括

这是一种ARF瘤抑制剂.

科学领域:

  • 在瘤学瘤学.
  • 分子生物学分子生物学
  • 生物化学 生物化学

背景情况:

  • 已知ARF瘤抑制剂在p53调节中的作用,但其p53/Mdm2独立的增长抑制机制需要阐明.
  • 了解ARF的瘤抑制途径对于开发向癌症治疗至关重要.

研究的目的:

  • 为了研究ARF介导的瘤抑制背后的分子机制.
  • 确定与ARF在体内相互作用的关键因素,并阐明它们在细胞生长调节中的作用.

主要方法:

  • 使用共免疫沉和体内关联研究来识别ARF相互作用蛋白质.
  • 评估ARF-BP1的乌比基连酶活性及其由ARF的抑制.
  • 在ARF-BP1失活后对p53-null和p53野生型细胞的细胞生长分析.
  • 研究ARF-BP1与p53.3的直接相互作用和无处不在的研究.

主要成果:

  • 鉴定出ARF-BP1,一种含有泛素酶的HECT动机,是与ARF相互作用的蛋白质.
  • ARF 抑制了 ARF-BP1 的泛素合酶活性.
  • 通过ARF-BP1无活化抑制了p53-null细胞的生长,模仿了ARF的诱导.
  • 在p53野生型细胞中,ARF-BP1直接在p53中化,其无活化对于ARF介导的p53稳定至关重要.

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结论:

  • ARF-BP1是ARF的p53-依赖和p53-独立瘤抑制功能的关键调解者.
  • ARF-BP1的双重作用表明它是各种癌症的潜在治疗点,无论p53状态如何.