Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary complex factor Elk-1.
Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary complex factor Elk-1.
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DOI：
10.1093/nar/gkn099
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发表时间：
2008-05
影响因子：
14.9
通讯作者：
Shaw PE
中科院分区：
文献类型：
--
作者：
Zhang HM;Li L;Papadopoulou N;Hodgson G;Evans E;Galbraith M;Dear M;Vougier S;Saxton J;Shaw PE
许多真核基因受到细胞外信号的剧烈调节。c-fos血清反应元件（SRE）通过血清反应因子（SRF）依赖性募集Elk-1（一种促分裂原活化蛋白激酶（MAPK）反应性转录因子）介导对促分裂原的转录激活。SRE启动子的后续事件如何刺激转录起始尚未完全解决。在这里，我们表明，细胞外信号调节激酶（ERK）和丝裂原和应激激活激酶（MSK）在体外和体内被招募到SRE启动子复合物。它们在体外的募集与Elk-1结合相关，并且对于ERK，Elk-1的D结构域/KIM特异性地参与。在体内，ERK和MSK的募集受到有丝分裂原的刺激，与组蛋白H3磷酸化相关，并受到Elk-1敲低的损害。免疫细胞化学和共聚焦显微镜显示，ERK似乎在一定程度上与启动，而不是延长RNA聚合酶II。两者合计，我们的数据增加了身体的证据表明，ERK和相关的MAPKs可能履行一个通用的角色，在启动子的急性调节基因。
Many eukaryotic genes are acutely regulated by extra-cellular signals. The c-fos serum response element (SRE) mediates transcriptional activation in response to mitogens through serum response factor (SRF)-dependent recruitment of Elk-1, a mitogen-activated protein kinase (MAPK)-responsive transcription factor. How subsequent events at SRE promoters stimulate initiation of transcription has yet to be fully resolved. Here we show that extra-cellular signal-regulated kinase (ERK) and mitogen and stress-activated kinase (MSK) are recruited to SRE promoter complexes in vitro and in vivo. Their recruitment in vitro correlates with Elk-1 binding and for ERK the D domain/KIM of Elk-1 is specifically involved. In vivo, recruitment of ERK and MSK is stimulated by mitogens, correlates with histone H3 phosphorylation and is impaired by Elk-1 knockdown. Immunocytochemistry and confocal microscopy reveal that ERK appears to associate to some extent with initiating rather than elongating RNA polymerase II. Taken together, our data add to the body of evidence implying that ERK and related MAPKs may fulfil a generic role at the promoters of acutely regulated genes.
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DOI：
10.1073/pnas.2035253100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Cantin, GT;Stevens, JL;Berk, AJ
通讯作者：
Berk, AJ
影响因子：
2.7
作者：
Chen, Fengming;Hancock, Chad N.;Shapiro, Paul
通讯作者：
Shapiro, Paul
影响因子：
16
作者：
Alepuz, PM;Jovanovic, A;Ammerer, G
通讯作者：
Ammerer, G
影响因子：
11.2
作者：
Aprelikova, Olga;Wood, Matthew;Barrett, J. Carl
通讯作者：
Barrett, J. Carl
影响因子：
10.5
作者：
Bardwell, L;Cook, JG;Thorner, J
通讯作者：
Thorner, J