雅普1在α-catenin的下游作用,控制表皮增殖
Karin Schlegelmilch1, Morvarid Mohseni, Oktay Kirak
1Stem Cell Program, Children's Hospital, Boston, MA 02115, USA.
Cell
|March 8, 2011
概括
雅普1是Hippo路径的关键组成部分,控制着表皮干细胞的增殖和哺乳动物皮肤中的组织生长. 阿尔法-素作为负调节剂,调节Yap1活动,并有助于"人群控制"机制.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 皮肤病学 皮肤病学
背景情况:
- 组织特异性干细胞的增殖在发育和再生过程中严格规范器官大小的确定.
- 控制这种控制的分子机制,特别是在皮肤中,尚未完全理解.
- 河马信号通路及其效应器Yap1是已知的细胞增殖和器官大小在各种情况下的调节者.
研究的目的:
- 为了研究Yap1的作用,Hippo通路的转录效应因子,在皮肤生物学中.
- 阐明Yap1调节表皮干细胞增殖和组织扩张的分子机制.
- 在皮肤恒温的背景下,确定Yap1的上游调节者.
主要方法:
- 使用功能增益和丧失研究来评估Yap1在表皮干细胞中的作用.
- 研究了Yap1与TEAD转录因子的相互作用.
- 分析了α-catenin对Yap1活性的调节作用,包括其酸化和与14-3-3和PP2A酸酶的相互作用.
主要成果:
- Yap1被确定为表皮干细胞增殖和皮肤组织扩张的关键调节器.
- Yap1通过与TEAD转录因子的相互作用来发挥其功能.
- 发现α-catenin是Yap1的上游负调节剂,通过调节与14-3-3和PP2A酸酶的相互作用来控制其活性和酸化状态.
结论:
- Yap1是哺乳动物皮肤上表皮干细胞增殖能力的关键决定因素.
- Yap1在控制组织大小的分子电路中起到重要作用,类似于"人群控制".
- α-catenin在调节Yap1活动方面发挥着重要作用,有助于感知皮肤中的细胞密度和瘤抑制.
更多相关视频
08:09CUBIC Protocol Visualizes Protein Expression at Single Cell Resolution in Whole Mount Skin Preparations
Published on: August 4, 2016
09:55All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
Published on: December 20, 2021
相关概念视频
Catenins
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
Mechanism of Lamellipodia Formation
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
The Ras Gene
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.
Ras is a superfamily...
Ras is a superfamily...
Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
