Retinoblastoma protein directly interacts with and activates the transcription factor NF-IL6
Retinoblastoma protein directly interacts with and activates the transcription factor NF-IL6
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DOI：
10.1073/pnas.93.1.465
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发表时间：
1996-01-09
影响因子：
11.1
通讯作者：
Lee, WH
中科院分区：
文献类型：
--
作者：
Chen, PL;Riley, DJ;Lee, WH
视网膜母细胞瘤蛋白（RB）在细胞分裂周期中的生物学功能已被广泛记录，但其在分化中的明显作用仍然很大程度上未被探索。为了研究 RB 如何参与分化，诱导 U937 大细胞淋巴瘤系沿单核细胞/巨噬细胞谱系分化。在分化过程中，发现 RB 通过其猿猴病毒 40 大肿瘤抗原 (T 抗原) 结合结构域与 NF-IL6（CAAT/增强子结合蛋白 (C/EBP) 转录因子家族的成员）直接相互作用。 NF-IL6 利用两个不同的区域在体外和细胞内与低磷酸化形式的 RB 结合。野生型而非突变型 RB 增强了 NF-IL6 与其同源 DNA 序列的体外结合活性以及细胞中 NF-IL6 的启动子反式激活。这些发现表明 RB 的一种新的生化功能：它通过明显的分子伴侣样活性激活对分化重要的特定转录因子。这与它对其他转录因子（例如 E2F-1）的隔离和失活形成鲜明对比，后者促进细胞周期的进展。这种不同的机制可能有助于解释 RB 在细胞分化和细胞分裂周期中的双重作用。
The biological function of the retinoblastoma protein (RB) in the cell division cycle has been extensively documented, but its apparent role in differentiation remains largely unexplored. To investigate how RB is involved in differentiation, the U937 large-cell lymphoma line was induced to differentiate along a monocyte/macrophage lineage, During differentiation RB was found to interact directly through its simian virus 40 large tumor antigen (T antigen)-binding domain with NF-IL6, a member of the CAAT/enhancer-binding protein (C/EBP) family of transcription factors. NF-IL6 utilizes two distinct regions to bind to the hypophosphorylated form of RB in vitro and in cells. Wild-type but not mutant RB enhanced both binding activity of NF-IL6 to its cognate DNA sequences in vitro and promoter transactivation by NF-IL6 in cells. These findings indicate a novel biochemical function of RB: it activates, by an apparent chaperone-like activity, specific transcription factors important for differentiation. This contrasts with its sequestration and inactivation of other transcription factors, such as E2F-1, which promote progression of the cell cycle, Such disparate mechanisms may help to explain the dual role of RB in cell differentiation and the cell division cycle.