A CD40 signalosome anchored in lipid rafts leads to constitutive activation of NF-κB and autonomous cell growth in B cell lymphomas
A CD40 signalosome anchored in lipid rafts leads to constitutive activation of NF-κB and autonomous cell growth in B cell lymphomas
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DOI：
10.1016/s1074-7613(01)00258-8
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发表时间：
2002-01-01
期刊：
影响因子：
32.4
通讯作者：
Ford, RJ
中科院分区：
文献类型：
--
作者：
Pham, LV;Tamayo, AT;Ford, RJ
B细胞系非霍奇金淋巴瘤（NHL-B）是显示出失调的B淋巴细胞生长特征的肿瘤性B细胞。与正常B细胞不同，侵袭性NHL-B细胞通过维持组装的支架样信号平台（称为脂筏微结构域内的信号体，从细胞膜延伸）显示核NF-κ B的组成型表达。CD 40信号体似乎是通过淋巴瘤细胞的CD 154（CD 40 L，gp 39）与CD 40的自体产生和同源结合而启动的。NHL-B中NF-κ B的组成型表达可以通过用抗CD 40或CD 154的抗体处理来下调，所述抗体破坏信号体、抑制淋巴瘤细胞生长并诱导细胞死亡。CD 40信号体可能为NHL-B细胞的治疗干预提供潜在的脆弱靶标。
B cell lineage non-Hodgkin's lymphomas (NHL-B) are neoplastic B cells that show dysregulated B lymphocyte growth characteristics. Unlike normal B cells, aggressive NHL-B cells show constitutive expression of nuclear NF-kappaB by maintaining an assembled, scaffold-like signaling platform, called a Signalosome within the lipid raft microdomain, extending from the cell membrane. The CD40 Signalosome appears to be initiated through autochthonous production and cognate binding of CD154 (CD40L, gp39) to CD40 by the lymphoma cell. Constitutive expression of NF-kappaB in NHL-B can be downregulated by treatment with antibodies to CD40 or CD154 that disrupt Signalosomes, inhibit lymphoma cell growth, and induce cell death. CD40 Signalosomes may provide a potentially vulnerable target for therapeutic intervention in NHL-B cells.