Hurst H C, Masson N, Jones N C, Lee K A
Gene Transcription Group, Imperial Cancer Research Fund, Hammersmith Hospital, London.
Mol Cell Biol. 1990 Dec;10(12):6192-203. doi: 10.1128/mcb.10.12.6192-6203.1990.
Promoter elements containing the sequence motif CGTCA are important for a variety of inducible responses at the transcriptional level. Multiple cellular factors specifically bind to these elements and are encoded by a multigene family. Among these factors, polypeptides termed activating transcription factor 43 (ATF-43) and ATF-47 have been purified from HeLa cells and a factor referred to as cyclic AMP response element-binding protein (CREB) has been isolated from PC12 cells and rat brain. We demonstrated that CREB and ATF-47 are identical and that CREB and ATF-43 form protein-protein complexes. We also found that the cis requirements for stable DNA binding by ATF-43 and CREB are different. Using antibodies to ATF-43 we have identified a group of polypeptides (ATF-43) in the size range from 40 to 43 kDa. ATF-43 polypeptides are related by their reactivity with anti-ATF-43, DNA-binding specificity, complex formation with CREB, heat stability, and phosphorylation by protein kinase A. Certain cell types vary in their ATF-43 complement, suggesting that CREB activity is modulated in a cell-type-specific manner through interaction with ATF-43. ATF-43 polypeptides do not appear simply to correspond to the gene products of the ATF multigene family, suggesting that the size of the ATF family at the protein level is even larger than predicted from cDNA-cloning studies.
含有序列基序CGTCA的启动子元件对于转录水平上的多种诱导反应很重要。多种细胞因子特异性结合这些元件,并由一个多基因家族编码。在这些因子中,被称为激活转录因子43(ATF - 43)和ATF - 47的多肽已从HeLa细胞中纯化出来,并且一种被称为环磷酸腺苷反应元件结合蛋白(CREB)的因子已从PC12细胞和大鼠脑中分离出来。我们证明了CREB和ATF - 47是相同的,并且CREB和ATF - 43形成蛋白质 - 蛋白质复合物。我们还发现ATF - 43和CREB稳定结合DNA的顺式要求是不同的。使用针对ATF - 43的抗体,我们鉴定出了一组分子量在40至43 kDa范围内的多肽(ATF - 43)。ATF - 43多肽在与抗ATF - 43的反应性、DNA结合特异性、与CREB形成复合物、热稳定性以及蛋白激酶A的磷酸化方面具有相关性。某些细胞类型的ATF - 43组成有所不同,这表明CREB活性通过与ATF - 43的相互作用以细胞类型特异性的方式受到调节。ATF - 43多肽似乎并不简单地对应于ATF多基因家族的基因产物,这表明ATF家族在蛋白质水平上的规模甚至比从cDNA克隆研究预测的还要大。