Serum regulation of Id1 expression by a BMP pathway and BMP responsive element.
Serum regulation of Id1 expression by a BMP pathway and BMP responsive element.
复制标题
DOI：
10.1016/j.bbagrm.2013.08.002
复制
发表时间：
2013-10
影响因子：
4.7
通讯作者：
Prywes, Ron
中科院分区：
文献类型：
--
作者：
Lewis, Thera C.;Prywes, Ron
关键词：
立即早期基因（IEGs）在血清刺激后静止细胞重新进入细胞周期时表达。这些基因参与生长控制和分化，因此它们的表达受到严格控制。许多IEG通过其启动子中的血清应答元件（SRE）进行调节，所述血清应答元件结合血清应答因子（SRF）。然而，许多其他IEG在其启动子中没有SRE，并且其血清调节知之甚少。我们已经在SRF耗尽的成纤维细胞中鉴定了SRF非依赖性IEGs。其中之一，Id 1，进行了更仔细的研究。我们在Id1启动子中定位了一个血清反应元件，发现它与BMP反应元件（BRE）相同。Id1 BRE对于Id1的血清调节是必要且充分的。通过siRNA耗尽Smad 4、用BMP拮抗剂头蛋白或BMP受体抑制剂dorsomorphin处理来抑制BMP途径阻断了Id1的血清诱导。此外，BMP 2足以诱导Id1表达。鉴于SRC抑制剂可以阻断Id1表达的报道，我们测试了SRC抑制剂AZD 0530，发现它抑制了Id1的血清激活。令人惊讶的是，这种抑制作用不依赖于SRC或其家族成员。相反，我们表明AZD 0530直接抑制BMP I型受体。Id1相关基因Id3的血清诱导也需要BMP途径。鉴于这些和其他研究结果，我们得出结论，Id家族的IEGs通过类似的BREs由血清中的BMP调节。这代表了血清调节IEG的第二途径。
Immediate Early Genes (IEGs) are expressed upon re-entry of quiescent cells into the cell cycle following serum stimulation. These genes are involved in growth control and differentiation and hence their expression is tightly controlled. Many IEGs are regulated through Serum Response Elements (SREs) in their promoters, which bind Serum Response Factor (SRF). However, many other IEGs do not have SREs in their promoters and their serum regulation is poorly understood. We have identified SRF-independent IEGs in SRF-depleted fibroblasts. One of these, Id1, was examined more closely. We mapped a serum responsive element in the Id1 promoter and find that it is identical to a BMP Responsive Element (BRE). The Id1 BRE is necessary and sufficient for the serum regulation of Id1. Inhibition of the BMP pathway by siRNA depletion of Smad 4, treatment with the BMP antagonist noggin, or the BMP receptor inhibitor dorsomorphin blocked serum induction of Id1. Further, BMP2 is sufficient to induce Id1 expression. Given reports that SRC inhibitors can block Id1 expression, we tested the SRC inhibitor, AZD0530, and found that it inhibits the serum activation of Id1. Surprisingly, this inhibition is independent of SRC or its family members. Rather, we show that AZD0530 directly inhibits the BMP type I receptors. Serum induction of the Id1 related gene Id3 also required the BMP pathway. Given these and other findings we conclude that the Id family of IEGs is regulated by BMPs in serum through similar BREs. This represents a second pathway for serum regulation of IEGs.
登录
查看更多内容
影响因子：
64.5
作者：
BENEZRA, R;DAVIS, RL;WEINTRAUB, H
通讯作者：
WEINTRAUB, H
影响因子：
4
作者：
Cen, B;Selvaraj, A;Prywes, R
通讯作者：
Prywes, R
影响因子：
11.2
作者：
Gautschi, Oliver;Tepper, Clifford G.;Kung, Hsing-Jien
通讯作者：
Kung, Hsing-Jien
影响因子：
64.8
作者：
HERRERA, RE;SHAW, PE;NORDHEIM, A
通讯作者：
NORDHEIM, A
影响因子：
7
作者：
Cooper, Sara J.;Trinklein, Nathan D.;Myers, Richard M.
通讯作者：
Myers, Richard M.