Transcriptional regulation by dimerization: Two sides to an incestuous relationship
Transcriptional regulation by dimerization: Two sides to an incestuous relationship
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二聚化的转录调控：乱伦关系的两个方面
DOI：
10.1016/0092-8674(90)90207-u
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发表时间：
1990
期刊：
影响因子：
64.5
通讯作者：
N. Jones
中科院分区：
文献类型：
--
作者：
N. Jones
转录调控涉及蛋白质因子与特定DNA序列元件的相互作用，这些元件在基因启动子内的排列决定了基因的转录模式。最近几年，序列特异性DNA结合蛋白的鉴定、表征和克隆取得了快速进展。许多特征性启动子元件不仅与一种特异性结合蛋白相互作用，而且与一个结构相关蛋白家族相互作用。该家族的规模可以惊人地大：哺乳动物JunlFos家族由至少六个成员组成（综述参见Kouzarides和Ziff，1989），并且ATFKREB家族具有至少七个成员（Hai等人，1989年）。许多因子以二聚体的形式与DNA结合，同一家族的不同成员以同源二聚体或异源二聚体的形式与同一家族的其他成员结合，这一发现使研究更加复杂，细胞中存在大量不同的复合物，这些复合物可以与特定的DNA序列元件结合，这表明DNA结合的竞争可能起着调节作用。如果复合物刺激转录的能力不同，则这是特别相关的。最近对Jun家族的两个成员JunA和JunB的研究强调了这种可能性（Chiu等人，1989; Schiitte等人，1989年）。这两种蛋白质与AP-1结合位点以同源二聚体或与Fos蛋白质以异源二聚体的形式结合。然而，结合的结果是显着不同的，因为JunA可以激活转录从一个启动子含有一个单一的AP-1网站，而JunB不能这样做。重要的是，JunB可以抑制JunA介导的激活，可能是通过竞争结合AP-1位点。这种干扰或抑制的生理作用尚不清楚，但很可能是重要的，因为JunA和JunB的相对水平在对各种刺激作出反应的细胞中可以显著不同。转录因子通常由具有不同结合或激活潜力的同源或异源二聚体组成的认识主要源于亮氨酸拉链蛋白的研究。拉链二聚化基序之前紧接着含有碱性残基簇的区域，并且拉链和碱性区域（bZIP结构域）都是DNA结合所需的。最初在转录因子C/EBP（一种结合CCAAT识别位点以及增强子核心序列的蛋白质）中鉴定的拉链的特征在于亮氨酸残基的七肽重复（Vinson等人，1989年，以及其中的参考文献）。物理研究表明，在二聚体形成过程中，这些区域采用卷曲螺旋结构，通过额外的疏水作用稳定，
Control of transcription involves the interaction of protein factors with specific DNA sequence elements, and the ar-ray of these elements within the promoter of a gene dictates its transcriptional pattern. The last few years have seen rapid progress in the identification, characterization, and cloning of sequence-specific DNA binding proteins. Many of the characterized promoter elements interact with not just one specific binding protein but a family of structurally related proteins. The size of the family can be surprisingly large: the mammalian JunlFos family consists of at least six members (for review, see Kouzarides and Ziff, 1989), and the ATFKREB family has at least seven members (Hai et al., 1989). Even more complexity is realized by the finding that many factors bind DNA as dimers, and different members of a family bind either as homodimers or as heterodimers with other members of the same family.The presence in a cell of a large repertoire of distinct complexes that can bind to a particular DNA sequence element suggests that competition for DNA binding may play a regulatory role. This is particularly relevant if the complexes differ in their ability to stimulate transcription. Such a possibility is emphasized by recent studies on two members of the Jun family, JunA and JunB (Chiu et al., 1989; Schiitte et al., 1989). Both proteins bind to the AP-1 binding site either as homodimers or as heterodimers with Fos protein. However, the consequences of binding are markedly different, since JunA can activate transcription from a promoter containing a single AP-1 site whereas JunB fails to do so. Importantly, JunB can repress JunA-mediated activation presumably by competition for binding to the AP-1 site. The physiological role of this interference or repression is not yet clear but is likely to be significant because the relative levels of JunA and JunB can differ markedly in cells responding to various stimuli. The ‘realization that transcription factors are often comprised of homo-or heterodimers that can have different binding or activation potential has emanated predominantly from the study of leucine zipper proteins. The zipper dimerization motif is immediately preceded by a region containing clusters of basic residues, and both the zipper and basic regions (the bZlP domain) are required for DNA binding. The zipper originally identified in the transcription factor C/EBP, a protein that binds to CCAAT recognition sites as well as enhancer core sequences, is characterized by heptad repeats of leucine residues (Vinson et al., 1989, and references therein). Physical studies suggest that during dimer formation these regions adopt a coiled coil structure stabilized by additional hydrophobic