Hateboer G, Gennissen A, Ramos Y F, Kerkhoven R M, Sonntag-Buck V, Stunnenberg H G, Bernards R
Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam.
EMBO J. 1995 Jul 3;14(13):3159-69. doi: 10.1002/j.1460-2075.1995.tb07318.x.
The adenovirus E1A gene products are nuclear phosphoproteins that can transactivate the other adenovirus early genes as well as several cellular genes, and can transform primary rodent cells in culture. Transformation and transactivation by E1A proteins is most likely to be mediated through binding to several cellular proteins, including the retinoblastoma gene product pRb, the pRb-related p107 and p130, and the TATA box binding protein TBP. We report here the cloning of BS69, a novel protein that specifically interacts with adenovirus 5 E1A. BS69 has no significant homology to known proteins and requires the region that is unique to the large (289R) E1A protein for high affinity binding. BS69 and E1A proteins coimmunoprecipitate in adenovirus-transformed 293 cells, indicating that these proteins also interact in vivo. BS69 specifically inhibits transactivation by the 289R E1A protein, but not by the 243R E1A protein. BS69 also suppressed the E1A-stimulated transcription of the retinoic acid receptor in COS cells, but did not affect the cellular E1A-like activity that is present in embryonic carcinoma cells. Our data indicate that BS69 is a novel and specific suppressor of E1A-activated transcription.
腺病毒E1A基因产物是核磷蛋白，可反式激活其他腺病毒早期基因以及一些细胞基因，并能在培养中转化原代啮齿动物细胞。E1A蛋白的转化和反式激活很可能是通过与几种细胞蛋白结合来介导的，这些细胞蛋白包括视网膜母细胞瘤基因产物pRb、与pRb相关的p107和p130，以及TATA盒结合蛋白TBP。我们在此报告一种与腺病毒5 E1A特异性相互作用的新型蛋白BS69的克隆。BS69与已知蛋白无明显同源性，并且高亲和力结合需要大（289R）E1A蛋白特有的区域。在腺病毒转化的293细胞中，BS69和E1A蛋白可共免疫沉淀，表明这些蛋白在体内也相互作用。BS69特异性抑制289R E1A蛋白的反式激活，但不抑制243R E1A蛋白的反式激活。BS69还抑制COS细胞中E1A刺激的视黄酸受体转录，但不影响胚胎癌细胞中存在的细胞E1A样活性。我们的数据表明，BS69是E1A激活转录的一种新型特异性抑制剂。
