Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany.
Biochem Biophys Res Commun. 2010 Oct 22;401(3):406-11. doi: 10.1016/j.bbrc.2010.09.067. Epub 2010 Sep 19.
Bag-1 consists in humans of four isoforms generated from the same RNA by alternative translation. Overexpression of single Bag-1 isoforms has identified Bag-1 as a negative regulator of action of many proteins including the glucocorticoid receptor (GR). Here we have analysed the ability of Bag-1 to regulate the transrepression function of the GR. Silencing Bag-1 expression only marginally affects the transrepression action of the GR but decreased the action of the transcription factor NF-κB. Furthermore phosphorylation and degradation of the inhibitor protein IκBα and nuclear accumulation of p65 and p50 NF-κB proteins in response to phorbol ester was attenuated following Bag-1 depletion in HeLa cells. Reconstitution of Bag-1 in depleted cells partially restored IκBα and NF-κB activation. Knock-down of Bag-1 expression also did not significantly alter GR-mediated transactivation but affected the basal transcription of some of the target genes. Thus Bag-1 proteins function as regulators of the action of selective transcription factors.
Bag-1 由同一 RNA 通过选择性翻译产生的四个同种型组成，在人类中存在。Bag-1 同种型的过表达已将 Bag-1 鉴定为多种蛋白质（包括糖皮质激素受体（GR））的活性的负调节剂。在这里，我们分析了 Bag-1 调节 GR 的转录抑制功能的能力。沉默 Bag-1 的表达仅略微影响 GR 的转录抑制作用，但降低了转录因子 NF-κB 的作用。此外，在用佛波酯处理后，Bag-1 耗尽的 HeLa 细胞中，抑制蛋白 IκBα 的磷酸化和降解以及 p65 和 p50 NF-κB 蛋白的核积累减弱。在耗尽的细胞中重建 Bag-1 部分恢复了 IκBα 和 NF-κB 的激活。Bag-1 表达的敲低也没有显著改变 GR 介导的转录激活，但影响了一些靶基因的基础转录。因此，Bag-1 蛋白作为选择性转录因子作用的调节剂。
