EWS-ATF-1 chimeric protein in soft tissue clear cell sarcoma associates with CREB-binding protein and interferes with p53-mediated trans-activation function
EWS-ATF-1 chimeric protein in soft tissue clear cell sarcoma associates with CREB-binding protein and interferes with p53-mediated trans-activation function
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DOI：
10.1038/sj.onc.1204684
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发表时间：
2001-10-11
期刊：
影响因子：
8
通讯作者：
Reddy, ESP
中科院分区：
文献类型：
--
作者：
Fujimura, Y;Siddique, H;Reddy, ESP
复发性t（12; 22）（q13; q12）与软组织透明细胞肉瘤相关的染色体易位导致嵌合蛋白EWS-ATF-1作为组成型转录激活因子。CBP/p300转录辅激活因子将多种转录因子连接到基础转录器上，参与转录激活、生长和细胞周期控制与分化。在这项研究中，我们表明，EWS-ATF-1协会组成CBP在体外和体内。EWS和ATF-1融合结构域都需要这种相互作用。在这里，我们证明，EWS-ATF-1抑制p53/CBP介导的反式激活功能。CBP的过表达可以抵消EWS-ATF-1的这种抑制作用。总之，这些发现表明EWS-ATF-1可能导致肿瘤的机制之一是通过靶向CBP/p300导致p53功能丧失。这种新的机制可能是导致这些和其他相关实体瘤发展的原因。
The recurrent t(12;22) (q13;q12) chromosomal translocation associated with soft tissue clear cell sarcoma results in a chimeric protein EWS-ATF-1 that acts as a constitutive transcriptional activator. The CBP/p300 transcriptional coactivator, which links various transcriptional factors to basal transcription apparatus, participates in transcriptional activation, growth and cell cycle control and differentiation. In this study, we show that EWS-ATF-1 associates constitutively with CBP both in vitro and in vivo. Both EWS and ATF-1 fusion domains are needed for this interaction. Here, we demonstrate that EWS-ATF-1 represses p53/CBP-mediated transactivation function. Overexpression of CBP can counteract this repressive effect of EWS-ATF-1. Taken together, these findings suggest that one of the mechanisms by which EWS-ATF-1 may cause tumors is through targeting CBP/p300 resulting in the loss of function of p53. This novel mechanism may be responsible for the development of these and other related solid tumors.