Choubey D, Li S J, Datta B, Gutterman J U, Lengyel P
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
EMBO J. 1996 Oct 15;15(20):5668-78.
Many of the antimicrobial, immunomodulatory and cell growth inhibitory activities of the interferons are mediated by interferon-inducible proteins. Earlier we characterized an interferon-inducible murine protein, p202, whose expression in transfected cells inhibits cell proliferation and which can form a complex with retinoblastoma protein (pRb). Here we report that in transfected cells expression of p202 inhibits E2F-stimulated transcription of a reporter gene and of endogenous genes. Inhibition of the transcriptional activity of E2F by p202 does not depend on fully functional pRb and is correlated with inhibition of the sequence-specific DNA binding of E2F. p202 interacts with the transcription factor E2F (E2F-1/DP-1) in vitro and in vivo. Inhibition of E2F activity by p202 may contribute to growth inhibition by the interferons.
干扰素的许多抗菌、免疫调节和细胞生长抑制活性是由干扰素诱导蛋白介导的。我们之前鉴定了一种干扰素诱导的小鼠蛋白p202,其在转染细胞中的表达会抑制细胞增殖,并且能与视网膜母细胞瘤蛋白(pRb)形成复合物。在此我们报告,在转染细胞中,p202的表达会抑制E2F刺激的报告基因和内源性基因的转录。p202对E2F转录活性的抑制不依赖于功能完全正常的pRb,且与E2F序列特异性DNA结合的抑制相关。p202在体外和体内均与转录因子E2F(E2F-1/DP-1)相互作用。p202对E2F活性的抑制可能有助于干扰素对生长的抑制作用。