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相关概念视频

Positive Regulator Molecules02:39

Positive Regulator Molecules

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Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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M-Cdk Drives Transition Into Mitosis02:15

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Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
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The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
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The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
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通过双T环酸化激活Cdk7的结构基础.

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概括

循环素依赖性激酶7 (Cdk7) 的双酸化调节了它的功能. S164酸化有助于复合体的形成,而T170增强了对转录基质的活性,如RNA聚合酶II.

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科学领域:

  • 分子生物学分子生物学
  • 生物化学 生化学
  • 结构生物学 结构生物学

背景情况:

  • 循环素依赖酶7 (Cdk7) 对于细胞循环进展和转录至关重要.
  • Cdk7作为CDK激活激酶 (CAK) 起作用,是转录因子TFIIH的一部分.
  • 在其激活段内,Cdk7的活动通过在T170和S164的酸化来调节.

研究的目的:

  • 阐明人类Cdk7/Cyclin H/Mat1复合体中双T环酸化的结构和功能作用.
  • 研究单个和组合酸化如何影响Cdk7的激酶活性和基质特异性.

主要方法:

  • 确定了人体Cdk7/Cyclin H/Mat1复合物的晶体结构,具有T170和S164酸化.
  • 评估的激酶活性和基质识别取决于单个和双T环酸化.
  • 在人类细胞中研究了S164和T170的酸化顺序.

主要成果:

  • 晶体结构显示了pT170协调保存的残留物,而ps164在三元复合体内形成了一个独特的氨酸网络.
  • CAK活性独立于T环酸化,但pT170显著增强了对非CDK基质的活性.
  • 双化刺激RNA聚合酶II CTD和SPT5 CTR的多位化.

结论:

  • 在人体细胞中,Cdk7的激活是一个连续的过程:S164酸化在T170酸化之前并可能是首要的.
  • pS164支持三方复合体的形成,并可能影响过程性.
  • pT170增强了Cdk7对关键转录基质的活性,突出显示了双酸化的调节作用.