Role of cellular tumor necrosis factor receptor-associated factors in NF-κB activation and lymphocyte transformation by herpesvirus Saimiri STP
Role of cellular tumor necrosis factor receptor-associated factors in NF-κB activation and lymphocyte transformation by herpesvirus Saimiri STP
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DOI：
10.1128/jvi.73.5.3913-3919.1999
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发表时间：
1999-05-01
影响因子：
5.4
通讯作者：
Jung, JU
中科院分区：
文献类型：
--
作者：
Lee, H;Choi, JK;Jung, JU
现在发现疱疹病毒松鼠猴（HVS）亚群A株11和亚群C株488的STP癌蛋白与肿瘤坏死因子受体相关因子（TRAF）1、2或3稳定相关。突变分析鉴定了STP-A11中PXQXT/S的残基对TRAF缔合至关重要。此外，STP-C488的一个稍微发散的区域对于TRAF缔合是至关重要的。突变分析还显示，STP-C488诱导NF-κ B B活化，这与其与TRAF相关的能力相关。HVS STP-C488 P-10-->R突变体在人T淋巴细胞转化为白细胞介素-2非依赖性生长方面存在缺陷，但在体外和体内显示出绒猴T淋巴细胞转化的野生型表型。STP-C488 P-10-->R突变体在Rat-1成纤维细胞转化中也有缺陷，成纤维细胞转化被TRAF 2显性阴性突变体阻断。这些数据表明TRAF参与STP-C488介导的人淋巴细胞和啮齿动物成纤维细胞转化。其他因子与普通绒猴T淋巴细胞的永生化有关，并且在人类淋巴细胞和啮齿动物成纤维细胞的转化中也可能是关键的。
The STP oncoproteins of the herpesvirus saimiri (HVS) subgroup A strain 11 and subgroup C strain 488 are now found to be stably associated with tumor necrosis factor receptor-associated factor (TRAF) 1, 2, or 3. Mutational analyses identified residues of PXQXT/S in STP-A11 as critical for TRAF association. In addition, a somewhat divergent region of STP-C488 is critical for TRAF association. Mutational analysis also revealed that STP-C488 induced NF-kappa B activation that was correlated with its ability to associate with TRAFs. The HVS STP-C488 P-10-->R mutant was deficient in human T-lymphocyte transformation to interleukin-2-independent growth but showed wild-type phenotype for marmoset T-lymphocyte transformation in vitro and in vivo. The STP-C488 P-10-->R mutant was also defective in Rat-1 fibroblast transformation, and fibroblast cell transformation was blocked by a TRAF2 dominant-negative mutant. These data implicate TRAFs in STP-C488-mediated transformation of human lymphocytes and rodent fibroblasts. Other factors are implicated in immortalization of common marmoset T lymphocytes and may also be critical in the transformation of human lymphocytes and rodent fibroblasts.