Sheppard K A, Rose D W, Haque Z K, Kurokawa R, McInerney E, Westin S, Thanos D, Rosenfeld M G, Glass C K, Collins T
Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Cell Biol. 1999 Sep;19(9):6367-78. doi: 10.1128/MCB.19.9.6367.
Nuclear factor-kappaB (NF-kappaB) plays a role in the transcriptional regulation of genes involved in inflammation and cell survival. In this report we demonstrate that NF-kappaB recruits a coactivator complex that has striking similarities to that recruited by nuclear receptors. Inactivation of either cyclic AMP response element binding protein (CREB)-binding protein (CBP), members of the p160 family of coactivators, or the CBP-associated factor (p/CAF) by nuclear antibody microinjection prevents NF-kappaB-dependent transactivation. Like nuclear receptor-dependent gene expression, NF-kappaB-dependent gene expression requires specific LXXLL motifs in one of the p160 family members, and enhancement of NF-kappaB activity requires the histone acetyltransferase (HAT) activity of p/CAF but not that of CBP. This coactivator complex is differentially recruited by members of the Rel family. The p50 homodimer fails to recruit coactivators, although the p50-p65 heterodimeric form of the transcription factor assembles the integrator complex. These findings provide new mechanistic insights into how this family of dimeric transcription factors has a differential effect on gene expression.
核因子-κB（NF-κB）在参与炎症和细胞存活的基因转录调控中发挥作用。在本报告中，我们证明NF-κB招募了一种共激活因子复合物，该复合物与核受体招募的复合物具有显著相似性。通过核抗体显微注射使环磷酸腺苷反应元件结合蛋白（CREB）结合蛋白（CBP）、p160共激活因子家族成员或CBP相关因子（p/CAF）失活，可阻止NF-κB依赖的反式激活。与核受体依赖的基因表达一样，NF-κB依赖的基因表达需要p160家族成员之一中的特定LXXLL基序，并且增强NF-κB活性需要p/CAF的组蛋白乙酰转移酶（HAT）活性，而不需要CBP的HAT活性。Rel家族成员对这种共激活因子复合物的招募存在差异。p50同二聚体无法招募共激活因子，尽管转录因子的p50-p65异二聚体形式可组装整合复合物。这些发现为这一二聚体转录因子家族如何对基因表达产生差异影响提供了新的机制见解。
