Transcriptional activation function of zinc finger protein TIS11 and its negative regulation by phorbol ester
Transcriptional activation function of zinc finger protein TIS11 and its negative regulation by phorbol ester
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DOI：
10.1006/bbrc.2000.3182
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发表时间：
2000-08-02
影响因子：
3.1
通讯作者：
Kaneda, N
中科院分区：
文献类型：
--
作者：
Murata, T;Hikita, K;Kaneda, N
TIS 11是一种CCCH锌指蛋白，是典型的生长因子诱导的核蛋白。我们发现，TIS 11具有激活转录的潜力时，融合到GAL 4 DNA结合域和瞬时共转染到大鼠嗜铬细胞瘤PC 12细胞沿着与GAL 4响应荧光素酶报告基因。对TIS 11缺失突变体的研究表明，主要的反式激活区域位于N-末端101个氨基酸残基，其余的中心和C-末端区域具有中等的反式激活活性。此外，TIS 11的反式激活活性被发现通过用佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）处理转染子而显著降低。PMA诱导的TIS 11失活可被蛋白激酶C抑制剂calphostin C和丝裂原活化蛋白（MAP）激酶抑制剂PD 98059阻断。这些结果表明，TIS 11的功能作为一个积极的转录调节和蛋白激酶C/MAP激酶信号级联参与负调控TIS 11由PMA（C）2000学术出版社。
TIS11, a CCCH zinc finger protein, is one of the typical growth factor-inducible nuclear proteins. We found that TIS11 possesses the potential to activate transcription when fused to the GAL4 DNA binding domain and transiently cotransfected into rat pheochromocytoma PC12 cells along with a GAL4-responsive luciferase reporter gene. The study with deletion mutants of TIS11 revealed that the major transactivation region is located at the N-terminal 101 amino acid residues and that the remaining central and C-terminal region had a moderate transactivational activity. In addition, the transactivational activity of TIS11 was found to be significantly reduced by treating the transfectants with phorbol 12-myristate 13-acetate (PMA). PMA-induced inactivation of TIS11 was blocked by calphostin C, a protein kinase C inhibitor, and PD98059, a mitogen-activated protein (MAP) kinase kinase inhibitor. These results suggested that TIS11 functions as a positive transcriptional regulator and that the protein kinase C/MAP kinase signaling cascade is involved in negative regulation of TIS11 by PMA (C) 2000 Academic Press.