MITF-M 表达与活性的转录后调控
中文名称
通路描述
黑色素细胞、神经元和胶质细胞均起源于来自神经嵴的细胞。决定神经元和胶质细胞分化的细胞较早且呈腹侧模式迁移，而决定黑色素细胞的细胞较晚离开神经嵴并呈背外侧模式迁移。尽管如此，黑色素细胞也可通过双 Schwann 细胞/黑色素细胞前体或 Schwann 细胞去分化（胶质细胞谱系衍生）途径产生（参见 Mort et al, 2015）。MITF-M 是黑色素细胞发育的关键调节因子，其表达区分了黑色素细胞命运与胶质和神经细胞命运。MITF-M 表达在细胞前体中被 FOXD3 和 SOX2 抑制。在不同物种中，这些转录因子可能直接结合 MITF-M 启动子元件以抑制转录，或通过独立于 DNA 结合的方式破坏促进转录活性的蛋白质 - 蛋白质相互作用（Nitzan et al, 2013a,b; Curran et al, 2009, 2010; Adameyko et al, 2012; 参见 Mort et al, 2015; White and Zon, 2008; Goding and Arnheiter, 2019）。FOXD3 和 SOX2 的表达本身受包括 ZIC1、PAX3、SNAIL2 和 SOX9 在内的其他转录因子级联调控（参见 Mort et al, 2015; Goding and Arnheiter, 2019）。FOXD3 介导的抑制解除部分依赖于 HDAC1 以及 SNAIL2 的下调（Ignatius et al, 2008; Greenhill et al, 2011; Nitzan et al, 2013a, b）。未着色但已分化的黑色素幼芽中的 MITF-M 表达依赖于 PAX3 和 SOX10 在启动子上的结合，以及 WNT、EDNRB 和 KIT 信号通路（参见 Mort et al, 2015; White and Zon, 2008; Goding and Arnheiter, 2019）。MITF-M 的初始表达还参与下调 FOXD3 和 SOX2，建立正反馈回路，从而强化对黑色素细胞命运的承诺（参见 Mort et al, 2015; Goding and Arnheiter, 2019）。除了转录调控外，MITF-M 的活性还受翻译后修饰控制，尽管这些修饰的意义并不总是明确。MAPK、WNT 和 AKT 信号通路下游的 SUMO 化、泛素化和磷酸化均可影响 MITF-M 的稳定性、定位或活性（参见 Goding and Arnheiter, 2019），而乙酰化则调节靶启动子的占据率，降低分化特异性启动子的占据率（Louphrasitthiphol et al, 2020, 2023）。
英文描述
Attachment and Entry This COVID-19 event has been created by a combination of computational inference (see https://reactome.org/documentation/inferred-events) from SARS-CoV-1 data and manual curation, as described in the summation for the overall SARS-CoV-2 infection pathway.
Coronavirus replication is initiated by the binding of S protein to the cell surface receptor(s). The S protein is composed of two functional domains, S1 (bulb) which mediates receptor binding and S2 (stalk) which mediates membrane fusion. Specific interaction between S1 and the cognate receptor triggers a drastic conformational change in S2, leading to fusion between the virus envelope and the cellular membrane and release of the viral nucleocapsid into the host cell cytosol. Receptor binding is the major determinant of the host range and tissue tropism for a coronavirus. Some human coronaviruses (HCoVs) have adopted cell surface enzymes as receptors, angiotensin converting enzyme 2 (ACE2) for SARS-CoV-2 (reviewed by Jackson et al, 2022), SARS-CoV-1, and HCoV NL63. The receptor-bound S protein is activated by cleavage into S1 and S2, mediated by one of two host proteases, the endosomal cysteine protease cathepsin L and another trypsin like serine protease. Type II transmembrane serine proteases TMPRSS2 and TMPRSS11D have also been implicated in the activation of S protein of SARS-CoV-2. Host factors may play additional roles in viral entry (not annotated here). Valosin containing protein (VCP) contributes by a poorly understood mechanism to the release of coronavirus from early endosomes. Host factors may also restrict the attachment and entry of HCoV.
Coronavirus replication is initiated by the binding of S protein to the cell surface receptor(s). The S protein is composed of two functional domains, S1 (bulb) which mediates receptor binding and S2 (stalk) which mediates membrane fusion. Specific interaction between S1 and the cognate receptor triggers a drastic conformational change in S2, leading to fusion between the virus envelope and the cellular membrane and release of the viral nucleocapsid into the host cell cytosol. Receptor binding is the major determinant of the host range and tissue tropism for a coronavirus. Some human coronaviruses (HCoVs) have adopted cell surface enzymes as receptors, angiotensin converting enzyme 2 (ACE2) for SARS-CoV-2 (reviewed by Jackson et al, 2022), SARS-CoV-1, and HCoV NL63. The receptor-bound S protein is activated by cleavage into S1 and S2, mediated by one of two host proteases, the endosomal cysteine protease cathepsin L and another trypsin like serine protease. Type II transmembrane serine proteases TMPRSS2 and TMPRSS11D have also been implicated in the activation of S protein of SARS-CoV-2. Host factors may play additional roles in viral entry (not annotated here). Valosin containing protein (VCP) contributes by a poorly understood mechanism to the release of coronavirus from early endosomes. Host factors may also restrict the attachment and entry of HCoV.
所含基因
11 个基因