FAS
小结
FAS编码蛋白是TNF受体超家族的成员，该受体包含一个death结构域，已被证明该受体在细胞程序性死亡的生理调控中起重要作用，并且已经涉及各种恶性肿瘤和免疫系统疾病的发病机理。该受体表明可以激活NF-kappaB，MAPK3/ERK1，和MAPK8/JNK，并且发现参与了正常二倍体成纤维细胞和T细胞中的转导增殖信号。与FAS相关的疾病包括自身免疫性淋巴组织增生综合征和淋巴组织增生综合征。
FAS, a death receptor that initiates apoptosis, is recurrently altered by mutation or downregulation in a diverse range of human cancers.FAS (also FAS1, CD95, APO-1) is a death receptor that mediates apoptosis. FAS binds the cognate ligand CD95L, a protein predominantly expressed on T and NK cells, resulting in the death of the associated cell expressing the FAS receptor. The FAS-CD95L interaction results in the formation of a death-inducing signaling complex that includes FADD, caspase 8, and caspase 10. Proteolytic processing of caspases then triggers a cascade that initiates apoptosis. FAS can also activate other downstream signaling cascades, including activation of the NF-KB and JNK pathways. Loss of FAS expression in several murine models of cancer, including ovarian and liver, results in reduced apoptosis and enhanced tumor growth. Germline mutations in FAS are associated with an autoimmune lymphoproliferative syndrome, a disorder associated with chronic lymphadenopathy and an increased risk of lymphoma development. Cell surface levels of FAS are frequently downregulated in cancer, allowing cells to evade programmed cell death. Somatic FAS mutations are also found in a variety of tumor types including multiple myeloma, lymphomas, T cell leukemias, and several solid tumor types. Mutations are frequently heterozygous and are predicted to be loss-of-function, allowing tumors to evade cell death via apoptosis.