Differential regulation of COX-2 transcription by Ras- and Rho-family of GTPases.
Differential regulation of COX-2 transcription by Ras- and Rho-family of GTPases.
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GTPases 的 Ras 和 Rho 家族对 COX-2 转录的差异调节。
DOI：
10.1006/bbrc.2000.3487
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Walsh,JH
中科院分区：
文献类型：
--
作者：
Slice,LW;Bui,L;Mak,C;Walsh,JH
环氧合酶-2（考克斯-2）基因的表达可被细胞因子、生长因子和肿瘤促进剂快速诱导，对炎症、血管生成具有重要意义，并且在各种癌细胞中显著增强。这些因子中的许多通过Ras和Rho家族小GTP酶启动信号传导。在这里，我们研究了Ras，Rac，Rho和Cdc 42 Hs在NIH 3 T3细胞中差异调节鼠考克斯-2启动子转录的能力。Ras、Rac、Rho的组成型活性突变体的过表达诱导了考克斯-2启动子的转录，但Cdc 42 Hs不诱导。Rac和Rho的反式激活需要位于考克斯-2启动子的-80和-40之间的顺式作用元件，而缺失该区域增强Ras的反式激活。位于-56的CRE/ATF元件对于Ras和Rac诱导的考克斯-2启动子的反式激活是关键的，但对于Rho的反式激活不是必需的。这证明了Rho依赖性的反式激活的考克斯-2启动子通过新的反式作用元件，并表明，在NIH 3 T3细胞中，由小GTP酶的信号转导，导致考克斯-2的表达不是通过一个顺序的途径从Cdc 42到Rac到Rho，而是通过独立的，平行的信号转导途径。
Cyclooxygenase-2 (Cox-2) gene expression which is rapidly induced by cytokines, growth factors and tumor promoters, is important for inflammation, angiogenesis, and is markedly enhanced in various cancer cells. Many of these factors initiate signaling through Ras- and Rho-family small GTPases. Here, we investigated the ability of Ras, Rac, Rho, and Cdc42Hs to differentially regulate transcription from the murine COX-2 promoter in NIH 3T3 cells. Over-expression of constitutively active mutants of Ras, Rac, Rho, but not Cdc42Hs induced transcription from the COX-2 promoter. Transactivation by Rac and Rho required cis-acting elements located between −80 and −40 of the COX-2 promoter whereas deletion of this region enhanced transactivation by Ras. A CRE/ATF element located at −56 was critical for Ras- and Rac-induced transactivation of the COX-2 promoter, but was not required for transactivation by Rho. This demonstrates Rho-dependent transactivation of the COX-2 promoter through novel trans-acting elements and suggests that, in NIH 3T3 cells, signaling by small GTPases that result in COX-2 expression is not through a sequential pathway from Cdc42 to Rac to Rho, but rather through independent, parallel signaling pathways.
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DOI：
10.1016/s0021-9258(18)98716-8
发表时间：
1991-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
B. Fletcher;R. Lim;B. Varnum;D. Kujubu;R. Koski;H. Herschman
通讯作者：
B. Fletcher;R. Lim;B. Varnum;D. Kujubu;R. Koski;H. Herschman
Gα13 刺激 Cyclooxygenase-2 启动子的 Rho 依赖性激活*
影响因子：
4.8
作者：
L. Slice;J. Walsh;E. Rozengurt
通讯作者：
E. Rozengurt
影响因子：
4.8
作者：
Morris, JK;Richards, JS
通讯作者：
Richards, JS
影响因子：
3.9
作者：
FENG, L;SUN, WQ;HWANG, D
通讯作者：
HWANG, D