Apo-3, a new member of the tumor necrosis factor receptor family, contains a death domain and activates apoptosis and NF-kappa B
Apo-3, a new member of the tumor necrosis factor receptor family, contains a death domain and activates apoptosis and NF-kappa B
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DOI：
10.1016/s0960-9822(02)70791-4
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发表时间：
1996-12-01
期刊：
影响因子：
9.2
通讯作者：
Ashkenazi, A
中科院分区：
文献类型：
--
作者：
Marsters, SA;Sheridan, JP;Ashkenazi, A
背景：迄今为止已经描述了两种包含所谓“死亡结构域”的受体：肿瘤坏死因子受体1 （TNFR1）和Fas/Apo-1 (CD95)；两者都属于TNFR基因家族。TNFR1的死亡结构域介导程序性细胞死亡（凋亡）和转录因子NF-kappa B的激活，而CD95的死亡结构域似乎只激活细胞凋亡。结果：我们确定了TNFR家族的另一个成员，我们将其命名为Apo-3。Apo-3是一种约47 kDa的跨膜蛋白，其细胞外富含半胱氨酸的结构域与TNFR家族成员相似。此外，Apo-3类似于TNFR1和CD95，因为它包含细胞质死亡结构域。Apo-3基因定位于人类染色体1p36.3，在脾脏、胸腺、外周血淋巴细胞、小肠和结肠等人体组织中检测到Apo-3 mRNA。Apo-3在HEK293或HeLa细胞中的异位表达可诱导明显的细胞凋亡。CrmA是一种痘病毒ced -3样蛋白酶抑制剂，可阻断TNFR1和CD95的死亡信号，抑制apo -3诱导的细胞凋亡。Apo-3的异位表达也诱导NF-kappa b的激活，Apo-3没有特异性地与Apo-2配体结合，表明Apo-3存在独特的配体。结论：这些结果确定了Apo-3是激活细胞凋亡的TNFR家族的第三个成员，并表明Apo-3、TNFR1和CD95参与了一个共同的凋亡细胞死亡机制。Apo-3类似于TNFR1，因为它可以刺激NF-kappa B活性并调节细胞凋亡。Apo-3 mRNA在多种组织中表达，这与该受体可能调节多种信号功能的可能性一致。
Background: Two receptors that contain the so-called 'death domain' have been described to date: tumor necrosis factor receptor 1 (TNFR1) and Fas/Apo-1 (CD95); both belong to the TNFR gene family. The death domain of TNFR1 mediates the activation of programmed cell death (apoptosis) and of the transcription factor NF-kappa B, whereas the death domain of CD95 only appears to activate apoptosis.Results: We have identified an additional member of the TNFR family, which we have named Apo-3. Apo-3 is a transmembrane protein of approximately 47 kDa that has similarity to members of the TNFR family in its extracellular, cysteine-rich domains. In addition, Apo-3 resembles TNFR1 and CD95 in that it contains a cytoplasmic death domain. The Apo-3 gene mapped to human chromosome 1p36.3, and Apo-3 mRNA was detected in several human tissues, including spleen, thymus, peripheral blood lymphocytes, small intestine and colon. Ectopic expression of Apo-3 in HEK293 or HeLa cells induced marked apoptosis. CrmA, a poxvirus inhibitor of Ced-3-like proteases which blocks death signaling by TNFR1 and CD95, inhibited Apo-3-induced apoptosis. Ectopic expression of Apo-3 also induced the activation of NF-kappa B. Apo-3 did not specifically bind to the Apo-2 ligand, suggesting the existence of a distinct ligand for Apo-3.Conclusions: These results identify Apo-3 as a third member of the TNFR family that activates apoptosis, and suggest that Apo-3, TNFR1 and CD95 engage a common apoptotic cell-death machinery. Apo-3 resembles TNFR1 because it can stimulate NF-kappa B activity and regulate apoptosis. Apo-3 mRNA is expressed in various tissues, consistent with the possibility that this receptor may regulate multiple signaling functions.