Identification and molecular cloning of AD5 E1B-55K associated proteins
Identification and molecular cloning of AD5 E1B-55K associated proteins
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AD5 E1B-55K 相关蛋白的鉴定和分子克隆
DOI：
10.1007/bf02559857
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发表时间：
1995
影响因子：
3.6
通讯作者：
H. Esche
中科院分区：
文献类型：
--
作者：
D. Brockmann;C. Bury;Gabriele Kröner;H. Kirch;H. Esche
早期1A区52R多肽是一种由体内致癌腺病毒亚型12专有表达的蛋白，可抑制由c-Jun-c-Jun同型二聚体组成的细胞转录因子复合物AP-1的反式激活功能。在本报告中，我们证明了体内的抑制与腺病毒蛋白与体外c-Jun的直接物理相互作用有关。有趣的是，52R蛋白与c-Jun的bZIP结构域结合，这对二聚化和DNA结合至关重要，但不与c-Jun的激活结构域结合。这种相互作用不会阻止c-Jun/AP-1的启动子结合。此外，c-Jun与TATA盒结合蛋白TBP之间的物理关联不受52R多肽的干扰。事实上，我们证明了腺病毒蛋白下调c-Jun活性是由于抑制了c-Jun反式激活域的磷酸化。体内c-Jun激活域的磷酸化是c-Jun与特定辅助因子（如CBP）相互作用所必需的，因此也是激活靶基因的先决条件。基于这些结果，我们提出了一个52R蛋白抑制c-Jun反式激活功能的模型，52R蛋白通过抑制c-Jun通过激活细胞转录因子所需的特定激酶的磷酸化来抑制c-Jun的反式激活功能。
The early region 1A 52R polypeptide, a protein expressed exclusively by the in vivo oncogenic adenovirus subtype 12, represses the trans-activating function of the cellular transcription factor complex AP-1 consisting of c-Jun-c-Jun homodimers. In this report we demonstrate that the repression in vivo correlates with a direct physical interaction of the adenovirus protein with c-Jun in vitro. Interestingly, the 52R protein binds to the bZIP domain of c-Jun essential for dimerization and DNA binding but not to the c-Jun activation domain. This interaction does not prevent the promoter binding of c-Jun/AP-1. Moreover, the physical association between c-Jun and the TATA box-binding protein TBP is not disturbed by the 52R polypeptide. In fact, we show evidence that down-regulation of c-Jun activity by the adenoviral protein is due to the inhibition of phosphorylation of the c-Jun trans-activation domain. In vivo phosphorylation of the c-Jun activation domain is necessary for the interaction of c-Jun with specific cofactors such as CBP and therefore a prerequisite for the activation of target genes. Due to these results we propose a model in which the 52R protein represses the trans-activating function of c-Jun by preventing its phosphorylation through a specific kinase necessary for the activation of the cellular transcription factor.
恶性细胞中 c-fos 和 c-jun 过度表达会降低其致瘤和转移潜力，并影响其 MHC I 类基因表达。
影响因子：
8
作者：
Yamit-Hezi,A;Plaksin,D;Eisenbach,L
通讯作者：
Eisenbach,L