Calkhoven C F, Ab G
Department of Biochemistry, University of Groningen, The Netherlands.
Biochem J. 1996 Jul 15;317 ( Pt 2)(Pt 2):329-42. doi: 10.1042/bj3170329.
This review focuses on the regulation of transcription factors, many of which are DNA-binding proteins that recognize cis-regulatory elements of target genes and are the most direct regulators of gene transcription. Transcription factors serve as integration centres of the different signal-transduction pathways affecting a given gene. It is obvious that the regulation of these regulators themselves is of crucial importance for differential gene expression during development and in terminally differentiated cells. Transcription factors can be regulated at two, principally different, levels, namely concentration and activity, each of which can be modulated in a variety of ways. The concentrations of transcription factors, as of intracellular proteins in general, may be regulated at any of the steps leading from DNA to protein, including transcription, RNA processing, mRNA degradation and translation. The activity of a transcription factor is often regulated by (de) phosphorylation, which may affect different functions, e.g. nuclear localization DNA binding and trans-activation. Ligand binding is another mode of transcription-factor activation. It is typical for the large super-family of nuclear hormone receptors. Heterodimerization between transcription factors adds another dimension to the regulatory diversity and signal integration. Finally, non-DNA-binding (accessory) factors may mediate a diverse range of functions, e.g. serving as a bridge between the transcription factor and the basal transcription machinery, stabilizing the DNA-binding complex or changing the specificity of the target sequence recognition. The present review presents an overview of different modes of transcription-factor regulation, each illustrated by typical examples.
本综述聚焦于转录因子的调控，其中许多是DNA结合蛋白，它们识别靶基因的顺式调控元件，是基因转录最直接的调控因子。转录因子作为影响特定基因的不同信号转导途径的整合中心。显然，这些调控因子自身的调控对于发育过程中和终末分化细胞中的差异基因表达至关重要。转录因子可在两个主要不同水平受到调控，即浓度和活性，每个水平都可以通过多种方式进行调节。转录因子的浓度，与一般细胞内蛋白质一样，可在从DNA到蛋白质的任何步骤中受到调控，包括转录、RNA加工、mRNA降解和翻译。转录因子的活性通常受（去）磷酸化调控，这可能影响不同功能，如核定位、DNA结合和反式激活。配体结合是转录因子激活的另一种模式。这在核激素受体的大型超家族中很典型。转录因子之间的异源二聚化给调控多样性和信号整合增添了另一维度。最后，非DNA结合（辅助）因子可能介导多种功能，例如作为转录因子与基础转录机制之间的桥梁，稳定DNA结合复合物或改变靶序列识别的特异性。本综述概述了转录因子调控的不同模式，每种模式都有典型例子说明。
