Binding of p300/CBP co-activators by polyoma large T antigen
Binding of p300/CBP co-activators by polyoma large T antigen
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DOI：
10.1074/jbc.m102906200
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发表时间：
2001-09-07
影响因子：
4.8
通讯作者：
Benjamin, TL
中科院分区：
文献类型：
--
作者：
Cho, SY;Tian, Y;Benjamin, TL
小 DNA 肿瘤病毒，例如猿猴病毒 40 (SV40) 和多瘤病毒 (Py)，利用宿主细胞蛋白来转录和复制其 DNA。病毒 T 抗原和宿主蛋白之间的相互作用导致细胞转化和肿瘤诱导。 SV40 的大 T 抗原与 p53、pRb/p107/p130 家族成员以及环 AMP 响应元件结合蛋白 (CREB) 结合蛋白 (CBP)/p300 相互作用。已知 Py 大 T 抗原仅与这些蛋白质中的 pRb 和 p300 相互作用。在这里，我们报告 Py large T 在体内和体外与 CBP 结合。在共转染测定中，Py large T 在 CREB 介导的反式激活中抑制 CBP/p300 的共激活功能，但在 NF-kappaB 介导的反式激活中不抑制。 p53 似乎不参与 CREB 介导的反式激活功能，并且对于大的 T:CBP 相互作用不是必需的。引入与腺病毒 EIA 和 SV40 大 T 同源的 Py 大 T 区域的突变可阻止与共激活剂的结合。这些突变的大 T 抗原无法抑制 CREB 介导的反式激活。 CBP/p300结合的Py突变体能够转化已建立的大鼠胚胎成纤维细胞，但在新生小鼠中诱导肿瘤的能力受到限制，这表明大T与共激活剂的相互作用可能对于病毒在完整宿主中复制和传播至关重要。
Small DNA tumor viruses such as simian virus 40 (SV40) and polyomavirus (Py) take advantage of host cell proteins to transcribe and replicate their DNA. Interactions between the viral T antigens and host proteins result in cell transformation and tumor induction. Large T antigen of SV40 interacts with p53, pRb/p107/ p130 family members, and the cyclic AMP-responsive element-binding protein (CREB)-binding protein (CBP)/ p300. Py large T antigen is known to interact only with pRb and p300 among these proteins. Here we report that Py large T binds to CBP in vivo and in vitro. In cotransfection assays, Py large T inhibits the co-activation functions of CBP/p300 in CREB-mediated transactivation but not in NF-kappaB-mediated transactivation. p53 appears not to be involved in the functions of CREB-mediated transactivation and is not essential for large T:CBP interaction. Mutations introduced into a region of Py large T with homology to adenovirus EIA and SV40 large T prevent binding to the co-activators. These mutant large T antigens fail to inhibit CREB-mediated transactivation. The CBP/p300-binding Py mutants are able to transform established rat embryo fibroblasts but are restricted in their ability to induce tumors in the newborn mouse, indicating that interaction of large T with the co-activators may be essential for virus replication and spread in the intact host.