CD30/TNF receptor-associated factor interaction: NF-kappa B activation and binding specificity

CD30/TNF receptor-associated factor interaction: NF-kappa B activation and binding specificity
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DOI:
10.1073/pnas.93.18.9699
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发表时间:
1996-09-03
影响因子:
11.1
通讯作者:
Choi, Y
Choi, Y
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lee, SY;Lee, SY;Choi, Y

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CD 30是肿瘤坏死因子(TNF)受体超家族的成员,CD 30在正常活化的淋巴细胞、几种病毒转化的T细胞或B细胞系以及霍奇金淋巴瘤的肿瘤细胞上表达,CD 30与其配体的相互作用诱导对细胞的多效性效应,导致增殖、分化或死亡,CD 30胞质尾区与TNF受体相关因子(TRAF)相互作用,后者已被证明可阻断TNF-R2和CD 40介导的信号。我们在此证明TRAF 2在CD 30诱导的NF-κ B B活化中也起重要作用,我们还表明TRAF 2介导的NF-κ B活化在由CD 30交联诱导的HIV转录活化中起作用。CD 30胞质尾区的详细定点突变揭示了TRAF有两个独立的结合位点,每个结合位点与TRAF的不同结构域相互作用。我们将CD 30中的TRAF-C结合位点定位于5-7个氨基酸的延伸。
CD30 is a member of the tumor necrosis factor (TNF) receptor superfamily, CD30 is expressed on normal activated lymphocytes, on several virally transformed T- or B-cell lines and on neoplastic cells of Hodgkin's lymphoma, The interaction of CD30 with its ligand induces pleiotropic effects on cells resulting in proliferation, differentiation, or death, The CD30 cytoplasmic tail interacts with TNF receptor-associated factors (TRAFs), which have been shown to transduce signals mediated by TNF-R2 and CD40, We demonstrate here that TRAF2 also plays an important role in CD30-induced NF-kappa B activation, We also show that TRAF2-mediated activation of NF-kappa B plays a role in the activation of HIV transcription induced by CD30 cross-linking, Detailed site-directed mutagenesis of the CD30 cytoplasmic tail reveals that there are two independent binding sites for TRAF, each interacting with a different domain of TRAF, Furthermore, we localized the TRAF-C binding site in CD30 to a 5-7 amino acid stretch.