Bcl3, an IκB protein, stimulates activating protein-1 transactivation and cellular proliferation
Bcl3, an IκB protein, stimulates activating protein-1 transactivation and cellular proliferation
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DOI：
10.1074/jbc.274.40.28491
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发表时间：
1999-10-01
影响因子：
4.8
通讯作者：
Lee, JW
中科院分区：
文献类型：
--
作者：
Na, SY;Choi, JE;Lee, JW
Bcl 3是一种I κ B蛋白，最初作为推定的原癌基因在B细胞慢性淋巴细胞性白血病的亚群中分离。随后显示Bcl 3与NF κ B B p50或p52同二聚体紧密结合并反式激活。在此，我们表明，Bcl-3刺激激活蛋白-1（AP-1）的反式激活，无论是单独或与转录整合类固醇受体辅激活因子-1和CREB结合蛋白/p300。酵母和哺乳动物双杂交试验以及谷胱甘肽S-转移酶下拉试验表明，Bcl 3的C-末端158个残基表现出自主的反式激活功能，并与AP-1组分c-Jun和c-Fos、CREB结合蛋白/p300和类固醇受体共激活因子-1的特定亚区相互作用。此外，抗HA抗体从共表达c-Jun和HA标记的Bcl 3的HeLa细胞中共沉淀c-Jun，这与Bcl 3在体内直接与AP-1缔合的想法一致。将Bcl-3表达载体显微注射到Rat-1成纤维细胞中，可显著提高AP-1的细胞靶基因c-jun的DNA合成和表达。这些结果表明，Bcl 3可能直接参与肿瘤发生过程中作为一种新的转录辅激活因子的促有丝分裂转录因子AP-1在体内。
Bcl3, an I kappa B protein, was originally isolated as a putative proto-oncogene in a subset of B cell chronic lymphocytic leukemias. Bcl3 was subsequently shown to associate tightly with and transactivate the NF kappa B p50 or p52 homodimer. Herein, we show that Bcl3 stimulates the activating protein-1 (AP-1) transactivation, either alone or in conjunction with transcription integrators steroid receptor coactivator-l and CREB-binding protein/p300. The C-terminal 158 residues of Bcl3 exhibited an autonomous transactivation function and interacted with specific subregions of the AP-1 components c-Jun and c-Fos, CREB-binding protein/p300, and steroid receptor coactivator-l, as demonstrated by the yeast and mammalian two-hybrid tests as well as glutathione S-transferase pull-down assays. In addition, anti-HA antibody co-precipitated c-Jun from HeLa cells co-expressing c-Jun and HA-tagged Bcl3, consistent with the idea that Bcl3 directly associates with AP-1 in vivo. Furthermore, microinjection of Bcl3 expression vector into Rat-1 fibroblast cells significantly enhanced DNA synthesis and expression of c-jun, one of the cellular target genes of AP-1. These results suggest that Bcl3 may directly participate in the tumorigenesis processes as a novel transcription coactivator of the mitogenic transcription factor AP-1 in vivo.