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首页> 外文期刊>Molecular and Cellular Biology >The amino-terminal transforming region of simian virus 40 large T and small t antigens functions as a J domain.
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The amino-terminal transforming region of simian virus 40 large T and small t antigens functions as a J domain.

机译：猿猴病毒40大T和小t抗原的氨基末端转化区起J结构域的作用。

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摘要

Simian virus 40 (SV40) encodes two proteins, large T antigen and small t antigen that contribute to virus-induced tumorigenesis. Both proteins act by targeting key cellular regulatory proteins and altering their function. Known targets of the 708-amino-acid large T antigen include the three members of the retinoblastoma protein family (pRb, p107, and p130), members of the CBP family of transcriptional adapter proteins (cap-binding protein [CBP], p300, and p400), and the tumor suppressor p53. Small t antigen alters the activity of phosphatase pp2A and transactivates the cyclin A promoter. The first 82 amino acids of large T antigen and small t antigen are identical, and genetic experiments suggest that an additional target(s) important for transformation interacts with these sequences. This region contains a motif similar to the J domain, a conserved sequence found in the DnaJ family of molecular chaperones. We show here that mutations within the J domain abrogate the ability of large T antigen to transform mammalian cells. To examine whether a purified 136-amino-acid fragment from the T antigen amino terminus acts as a DnaJ-like chaperone, we investigated whether this fragment stimulates the ATPase activity of two hsc70s and discovered that ATP hydrolysis is stimulated four- to ninefold. In addition, ATPase-defective mutants of full-length T antigen, as well as wild-type small t antigen, stimulated the ATPase activity of hsc70. T antigen derivatives were also able to release an unfolded polypeptide substrate from an hsc70, an activity common to DnaJ chaperones. Because the J domain of T antigen plays essential roles in viral DNA replication, transcriptional control, virion assembly, and tumorigenesis, we conclude that this region may chaperone the rearrangement of multiprotein complexes.
机译：猿猴病毒40（SV40）编码两种蛋白，大T抗原和小T抗原，它们有助于病毒诱导的肿瘤发生。两种蛋白都通过靶向关键的细胞调节蛋白并改变其功能来发挥作用。 708个氨基酸的大T抗原的已知靶标包括成视网膜细胞瘤蛋白家族的三个成员（pRb，p107和p130），转录衔接蛋白CBP家族的成员（帽结合蛋白[CBP]，p300，和p400），以及抑癌药物p53。小的t抗原会改变磷酸酶pp2A的活性，并反激活细胞周期蛋白A启动子。大T抗原和小T抗原的前82个氨基酸是相同的，并且遗传实验表明，对于转化重要的另外的靶标与这些序列相互作用。该区域包含类似于J结构域的基序，J结构域是分子伴侣的DnaJ家族中发现的保守序列。我们在这里显示J域内的突变消除了大T抗原转化哺乳动物细胞的能力。若要检查从T抗原氨基末端纯化的136个氨基酸片段是否充当DnaJ状分子伴侣，我们研究了该片段是否刺激了两个hsc70s的ATPase活性，并发现ATP水解被刺激了四到九倍。此外，全长T抗原的ATPase缺陷型突变体以及野生型小t抗原刺激了hsc70的ATPase活性。 T抗原衍生物还能够从hsc70释放未折叠的多肽底物，这是DnaJ分子伴侣共有的活性。由于T抗原的J结构域在病毒DNA复制，转录控制，病毒体装配和肿瘤发生中起着至关重要的作用，因此我们得出结论，该区域可能陪伴多蛋白复合物的重排。

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