Virbasius C M, Wagner S, Green M R
Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605, USA.
Mol Cell. 1999 Aug;4(2):219-28. doi: 10.1016/s1097-2765(00)80369-x.
We have identified and cloned a human nuclear protein that dramatically increases DNA binding of transcription factors that contain a basic region-leucine zipper (bZIP) DNA binding domain. We show that this bZIP enhancing factor (BEF) functions as a molecular chaperone. BEF stimulates DNA binding by recognizing the unfolded leucine zipper and promoting the folding of bZIP monomers to dimers; the elevated concentration of the bZIP dimer then drives the DNA binding reaction. Antisense experiments indicate that BEF is required for efficient transcriptional activation by bZIP proteins in vivo. Our results reveal protein folding in the nucleus as a step at which sequence-specific DNA binding proteins can be regulated.
我们已经鉴定并克隆了一种人类核蛋白，它能显著增强含有碱性区域-亮氨酸拉链（bZIP）DNA结合结构域的转录因子与DNA的结合。我们发现这种bZIP增强因子（BEF）作为一种分子伴侣发挥作用。BEF通过识别未折叠的亮氨酸拉链并促进bZIP单体折叠成二聚体来刺激DNA结合；bZIP二聚体浓度的升高进而驱动DNA结合反应。反义实验表明，BEF是bZIP蛋白在体内有效转录激活所必需的。我们的结果揭示了细胞核中的蛋白质折叠是一个可以调控序列特异性DNA结合蛋白的步骤。
