Inhibition of E2F-4/DP-1-stimulated transcription by p202
Inhibition of E2F-4/DP-1-stimulated transcription by p202
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DOI：
10.1038/sj.onc.1201184
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发表时间：
1997-07-17
期刊：
影响因子：
8
通讯作者：
Gutterman, JU
中科院分区：
文献类型：
--
作者：
Choubey, D;Gutterman, JU
干扰素（IFN）诱导蛋白介导干扰素的活性，包括细胞生长调节活性。我们已经证明，p202，一个IFN-诱导的52 kDa主要核磷蛋白，其在转染细胞中的表达抑制细胞增殖，与视网膜母细胞瘤肿瘤抑制蛋白（pRb）和转录因子E2 F（E2 F-1/DP-1）在体外和体内相互作用。显示p202抑制E2 F-1/DP-1刺激的报告基因和内源基因的转录。在这里，我们报告，p202的表达抑制E2 F-4/DP-1刺激的报告基因在转染细胞中的转录。此外，这种抑制与抑制E2 F-4的序列特异性DNA结合有关，E2 F-4与口袋蛋白p107或p130复合，并在体外以其“游离”形式存在。p202在体外和体内与p107和p130结合，并且还与E2 F-4结合，支持含有p107/E2 F-4或p130/E2 F-4和p202的复合物存在于体内的观点。此外，E2 F-4编码质粒在AKR-2B细胞中的共转染克服了p202介导的细胞生长抑制，提高了p202至少部分通过调节E2 F-4介导的转录而有助于干扰素抑制细胞生长的可能性。
The interferon (IFN)-inducible proteins mediate activities of the interferons including the cell growth-regulatory activity. We have shown that p202, an IFN-inducible 52kDa primarily nuclear phosphoprotein whose expression in transfected cells inhibits cell proliferation, interacts with the retinoblastoma tumor suppressor protein (pRb) and the transcription factor E2F (E2F-1/DP-1) in vitro and in vivo. p202 was shown to inhibit E2F-1/DP-1-stimulated transcription of a reporter gene and of endogenous genes. Here we report that expression of p202 inhibited E2F-4/DP-1-stimulated transcription of a reporter gene in transfected cells. Furthermore, this inhibition was associated with the inhibition of the sequence-specific DNA-binding of E2F-4 both in complex with the pocket proteins p107 or p130 and in its 'free' form in vitro. p202 bound to p107 and p130 in vitro and in vivo and also associated with E2F-4, supporting the notion that complexes containing p107/E2F-4 or p130/E2F-4 and p202 exist in vivo. Moreover, cotransfection of E2F-4-encoding plasmid in AKR-2B cells overcame p202-mediated inhibition of cell growth, raising the possibility that p202 contributes to cell growth inhibition by the interferons, at least in part, by modulating E2F-4-mediated transcription.