Baeuerle P A, Baltimore D
Whitehead Institute for Biomedical Research, MA 02142.
Science. 1988 Oct 28;242(4878):540-6. doi: 10.1126/science.3140380.
In cells that do not express immunoglobulin kappa light chain genes, the kappa enhancer binding protein NF-kappa B is found in cytosolic fractions and exhibits DNA binding activity only in the presence of a dissociating agent such as sodium deoxycholate. The dependence on deoxycholate is shown to result from association of NF-kappa B with a 60- to 70-kilodalton inhibitory protein (I kappa B). The fractionated inhibitor can inactivate NF-kappa B from various sources--including the nuclei of phorbol ester-treated cells--in a specific, saturable, and reversible manner. The cytoplasmic localization of the complex of NF-kappa B and I kappa B was supported by enucleation experiments. An active phorbol ester must therefore, presumably by activation of protein kinase C, cause dissociation of a cytoplasmic complex of NF-kappa B and I kappa B by modifying I kappa B. this releases active NF-kappa B which can translocate into the nucleus to activate target enhancers. The data show the existence of a phorbol ester-responsive regulatory protein that acts by controlling the DNA binding activity and subcellular localization of a transcription factor.
在不表达免疫球蛋白κ轻链基因的细胞中，κ增强子结合蛋白NF-κB存在于胞质组分中，并且仅在存在诸如脱氧胆酸钠等解离剂的情况下才表现出DNA结合活性。对脱氧胆酸钠的依赖性被证明是由于NF-κB与一种60至70千道尔顿的抑制蛋白（IκB）结合所致。分级分离的抑制剂能够以特异性、饱和且可逆的方式使来自各种来源（包括佛波酯处理细胞的细胞核）的NF-κB失活。去核实验支持了NF-κB与IκB复合物的胞质定位。因此，一种活性佛波酯大概是通过激活蛋白激酶C，通过修饰IκB导致NF-κB与IκB的胞质复合物解离。这释放出活性NF-κB，其可转运至细胞核以激活靶增强子。数据表明存在一种佛波酯反应性调节蛋白，其通过控制转录因子的DNA结合活性和亚细胞定位发挥作用。
