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相关概念视频

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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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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Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
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Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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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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Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
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在METTL3-依赖的m.

Shuo Wan1,2,3, Yadong Sun2, Jinbao Zong4

  • 1The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.

Cell death & disease
|June 3, 2023
PubMed
概括
此摘要是机器生成的。

依赖METTL3的m6A甲基化对于女性的生育能力至关重要. 它的缺乏通过破坏雌激素和孕激素信号来损害子宫的受体性和决定性,从而提供了对不孕症原因的见解.

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科学领域:

  • 生殖生物学 生殖生物学
  • 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
  • 分子内分泌学分子内分泌学

背景情况:

  • 不孕症影响全球数百万人,许多原因尚不清楚.
  • 表观遗传调节,包括m6A修饰,在繁殖中越来越被认可.
  • 在此之前,m6A甲基化对女性生育能力的具体作用尚不清楚.

研究的目的:

  • 研究METTL3依赖的m6A甲基化在女性生育能力中的作用.
  • 探索m6A修饰影响生殖健康的机制.
  • 为了确定不孕不育的潜在治疗点.

主要方法:

  • 对不孕妇女METTL3表达的GEO数据集的分析.
  • 条件删除Mettl3在小鼠的雌性生殖道 (Pgr-Cre驱动器).
  • 对子宫的m6A-seq分析以确定m6A修饰基因.
  • 在体外实验中对Myc过度表达的实验.

主要成果:

  • 在不孕妇女的子宫中,METTL3的表达下调.
  • 在小鼠中,Mettl3的删除会导致不孕,子宫受体受损和决定性.
  • METTL3影响雌激素反应基因 (例如,Elf3,Celsr2) 的稳定性,并损害孕激素信号传递 (PR,Myc).
  • 在Mettl3缺乏的小鼠中,Myc过度表达部分挽救了决定性缺陷.

结论:

  • 依赖METTL3的m6A甲基化对女性生育能力至关重要.
  • 它在子宫内膜中平衡雌激素和孕的信号传递.
  • 这项研究提供了关于不孕症病原和潜在管理策略的见解.