Activation of gene expression by metal-responsive signal transduction pathways.
Activation of gene expression by metal-responsive signal transduction pathways.
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DOI：
10.1289/ehp.02110s5813
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发表时间：
2002-10
影响因子：
10.4
通讯作者：
Freedman JH
中科院分区：
文献类型：
--
作者：
Adams TK;Saydam N;Steiner F;Schaffner W;Freedman JH
金属硫蛋白是一种小的、富含半胱氨酸的金属结合蛋白，在维持细胞内金属稳态和过渡金属解毒中起重要作用。MTF-1（金属转录因子-1）在调节金属诱导的金属硫蛋白转录激活中起核心作用。在这里，我们报道了MTF-1的磷酸化在MTF-1/金属响应元件介导的转录激活中起关键作用。抑制剂研究表明，信号转导级联反应，包括由蛋白激酶C、酪氨酸激酶和酪蛋白激酶II介导的信号转导级联反应，对锌和镉诱导的转录至关重要。此外，钙信号还参与调控转录。相反，camp依赖性蛋白激酶可能不直接参与金属反应。与其他转录因子的报道相反，转录激活的抑制不会损害MTF-1与DNA的结合，这表明磷酸化不会调节DNA的结合。在蛋白激酶C抑制的条件下，MTF-1的磷酸化水平升高，表明该转录因子的去磷酸化介导了其激活。
Metallothioneins are small, cysteine-rich, metal-binding proteins that play important roles in maintaining intracellular metal homeostasis and in transition metal detoxification. MTF-1 (metal transcription factor-1) plays a central role in regulating the metal-inducible, transcriptional activation of metallothionein. Here we report that the phosphorylation of MTF-1 plays a critical role in the activation of MTF-1/metal-responsive element-mediated transcription. Inhibitor studies indicate that signal transduction cascades, including those mediated by protein kinase C, tyrosine kinase, and casein kinase II, are essential for zinc- and cadmium-inducible transcription. In addition, calcium signaling is also involved in regulating transcription. In contrast, cAMP-dependent protein kinase may not be directly involved in the metal response. Contrary to what has been reported for other transcription factors, the inhibition of transcriptional activation does not impair the binding of MTF-1 to DNA, suggesting that phosphorylation is not regulating DNA binding. Elevated phosphorylation of MTF-1 is observed under conditions of protein kinase C inhibition, suggesting that dephosphorylation of this transcription factor mediates its activation.
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DOI：
10.1016/s1532-0456(01)00165-x
发表时间：
2001-03-01
影响因子：
3.9
作者：
Hermesz, E;Abrahám, M;Nemcsók, J
通讯作者：
Nemcsók, J
DOI：
10.1073/pnas.91.4.1219
发表时间：
1994-02-15
影响因子：
11.1
作者：
PALMITER, RD
通讯作者：
PALMITER, RD
DOI：
10.1111/j.1749-6632.1998.tb08987.x
发表时间：
1998-01-01
期刊：
STRESS OF LIFE
影响因子：
--
作者：
Karin, M
通讯作者：
Karin, M
影响因子：
6.1
作者：
ARIZONO, K;PETERSON, KL;BRADY, FO
通讯作者：
BRADY, FO
影响因子：
2.9
作者：
KAGI, JHR;SCHAFFER, A
通讯作者：
SCHAFFER, A