Fas/Fas L信號(hào)通路圖
細(xì)胞凋亡專題
Fas/Fas L信號(hào)通路 最早被證明在細(xì)胞凋亡 中起著重要的作用。Fas是一種跨膜蛋白,屬于腫瘤壞死因子受體超家族成員,它與FasL結(jié)合可以啟動(dòng)凋亡信號(hào)的轉(zhuǎn)導(dǎo)引起細(xì)胞凋亡 。它的活化包括一系列步驟:首先配體誘導(dǎo)受體三聚體化,然后在細(xì)胞膜 上形成凋亡誘導(dǎo)復(fù)合物,這個(gè)復(fù)合物中包括帶有死亡結(jié)構(gòu)域的Fas相關(guān)蛋白FADD。Fas一旦和配體FasL結(jié)合,可通過(guò)Fas分子 啟動(dòng)致死性信號(hào)轉(zhuǎn)導(dǎo),最終引起細(xì)胞一系列特征性變化,使細(xì)胞死亡。
Receptors in the TNF receptor family are associated with the induction of apoptosis, as well as inflammatory signaling. The Fas receptor (CD95) mediates apoptotic signaling by Fas-ligand expressed on the surface of other cells. The Fas-FasL interaction plays an important role in the immune system and lack of this system leads to autoimmunity, indicating that Fas-mediated apoptosis removes self-reactive lymphocytes. Fas signaling is also involved in immune surveillance to remove transformed cells and virus infected cells. Binding of FAS to oligimerized FasL on another cell activates apoptotic signaling through a cytoplasmic domain termed the death domain that interacts with signaling adaptors including FAF, FADD and DAX to activate the caspase proteolytic cascade. Caspase-8 and caspase-10 are first activated, to then cleave and activate downstream caspases, and a variety of cellular substrates that lead to cell death. Caspases cleave nuclear lamins, causing the nucleus to break down and lose its normal structure and another caspase substrate is DFF, inducing cleavage and degradation of the genome. Other caspase substrates are involved in cytoskeletal structure, cell cycle regulation and signaling pathways. Activation of JNK kinase, activation of Jun, and production of ceramide may also play roles in Fas-mediated apoptosis. Activation of fas-mediated apoptosis is opposed by I-FLICE and FAP. Viruses and tumors may escape immune surveillance in part through suppression of fas-mediated apoptosis using similar mechanisms.
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