染色质结合的 IκBα 在分化和癌症中调节一组 Polycomb 靶基因。
Chromatin-bound IκBα regulates a subset of polycomb target genes in differentiation and cancer.
机构信息
Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona 08003, Spain.
出版信息
Cancer Cell. 2013 Aug 12;24(2):151-66. doi: 10.1016/j.ccr.2013.06.003. Epub 2013 Jul 11.
Abstract
IκB proteins are the primary inhibitors of NF-κB. Here, we demonstrate that sumoylated and phosphorylated IκBα accumulates in the nucleus of keratinocytes and interacts with histones H2A and H4 at the regulatory region of HOX and IRX genes. Chromatin-bound IκBα modulates Polycomb recruitment and imparts their competence to be activated by TNFα. Mutations in the Drosophila IκBα gene cactus enhance the homeotic phenotype of Polycomb mutants, which is not counteracted by mutations in dorsal/NF-κB. Oncogenic transformation of keratinocytes results in cytoplasmic IκBα translocation associated with a massive activation of Hox. Accumulation of cytoplasmic IκBα was found in squamous cell carcinoma (SCC) associated with IKK activation and HOX upregulation.
摘要
IκB 蛋白是 NF-κB 的主要抑制剂。在这里，我们证明了 SUMO 化和磷酸化的 IκBα 在角质形成细胞的核内积累，并与 HOX 和 IRX 基因调节区域的组蛋白 H2A 和 H4 相互作用。染色质结合的 IκBα 调节 Polycomb 的募集，并赋予它们被 TNFα 激活的能力。果蝇 IκBα 基因 cactus 的突变增强了 Polycomb 突变体的同源异形表型，而这不能被 dorsal/NF-κB 的突变所抵消。角质形成细胞的致癌转化导致与 Hox 大量激活相关的细胞质 IκBα易位。在与 IKK 激活和 HOX 上调相关的鳞状细胞癌 (SCC) 中发现了细胞质 IκBα的积累。
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