Lee H, Choi J K, Li M, Kaye K, Kieff E, Jung J U
Department of Microbiology and Molecular Genetics, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102, USA.
J Virol. 1999 May;73(5):3913-9. doi: 10.1128/JVI.73.5.3913-3919.1999.
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-kappaB activation that was correlated with its ability to associate with TRAFs. The HVS STP-C488 P10-->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 P10-->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.
现已发现，疱疹病毒猴痘（HVS）A亚组11株和C亚组488株的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。突变分析确定STP-A11中PXQXT/S残基对于TRAF结合至关重要。此外，STP-C488的一个略有不同的区域对于TRAF结合也至关重要。突变分析还显示，STP-C488诱导的核因子κB激活与其与TRAFs结合的能力相关。HVS STP-C488 P10→R突变体在人T淋巴细胞向白细胞介素-2非依赖性生长的转化中存在缺陷，但在体外和体内对狨猴T淋巴细胞转化表现出野生型表型。STP-C488 P10→R突变体在大鼠-1成纤维细胞转化中也存在缺陷，而成纤维细胞转化被TRAF2显性负性突变体阻断。这些数据表明TRAFs参与了STP-C488介导的人淋巴细胞和啮齿动物成纤维细胞的转化。其他因素与普通狨猴T淋巴细胞的永生化有关，也可能在人淋巴细胞和啮齿动物成纤维细胞的转化中起关键作用。
