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核因子κB(nuclear factor-κB,NF-κB)参与转录调控许多与细胞生长、凋亡、肿瘤形成和转移、胚胎发育及炎症反应相关的基因.它的二聚体与抑制蛋白结合,如抑制蛋白κB(IκBα,β或γ),而被滞留在细胞质中处于失活状态.然而NF-κB是否还有其它的抑制因子目前还不清楚.本研究结果表明,SIP(steroid receptor coactivator,SRC,SRC-interacting protein)是NF-κB家族的一个新抑制因子,它通过PEST结构域与NF-κB家族的p65蛋白相互作用.当细胞处于静息状态时,SIP将p65蛋白隔离于细胞质中;当有刺激因子TNFα或IL-1作用时,SIP与p65解离继而使p65进入细胞核启动下游靶基因转录激活.该研究为进一步认识NF-κB介导基因转录调控机制和相关疾病的发生发展提供了重要的理论依据.
Nuclear factor-κB (NF-κB) is involved in the transcriptional regulation of many genes involved in cell growth, apoptosis, tumorigenesis and metastasis, embryonic development, and inflammatory responses. Its dimers bind to inhibitory proteins such as inhibitory However, it is unclear whether NF-κB has other inhibitory factors.Our results show that SIP (steroid receptor coactivator, SRC, β, γ) is inactive in cytoplasm, SRC-interacting protein, a novel inhibitor of NF-κB family, interacts with the NF-κB family of p65 proteins through the PEST domain. When the cells are resting, SIP isolates the p65 protein in the cytoplasm. When When stimulated by TNFα or IL-1, SIP dissociates from p65 and then p65 enters the nucleus to initiate the transcriptional activation of downstream target genes.This study provides a further understanding of the mechanism of NF-κB-mediated gene transcription and related diseases Important theoretical basis.