REGULATION OF THE ETS-RELATED TRANSCRIPTION FACTOR ELF-1 BY BINDING TO THE RETINOBLASTOMA PROTEIN
REGULATION OF THE ETS-RELATED TRANSCRIPTION FACTOR ELF-1 BY BINDING TO THE RETINOBLASTOMA PROTEIN
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DOI：
10.1126/science.8493578
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发表时间：
1993-05-28
期刊：
影响因子：
56.9
通讯作者：
LEIDEN, JM
中科院分区：
文献类型：
--
作者：
WANG, CY;PETRYNIAK, B;LEIDEN, JM
视网膜母细胞瘤基因产物(Rb)是一种核磷蛋白，调节细胞周期进程。ELF-1是一种淋巴特异的ETS转录因子，在T细胞激活过程中调节可诱导基因的表达。在这份报告中，Elf-1包含一个序列基序，该基序与几种病毒癌蛋白的Rb结合部位高度相关，并在体外和体内都与Rb的口袋区域结合。ELF-1仅与低磷酸化形式的Rb结合，而不能与来自视网膜母细胞瘤患者的Rb突变体结合。免疫共沉淀实验证明Elf-1和Rb在静息的正常人T细胞中存在关联。在T细胞激活后，Rb的磷酸化导致Elf-1的释放，这与Elf-1介导的转录激活在时间上是相关的。在T细胞激活过程中，磷酸化缺陷形式的Rb的过表达抑制了Elf-1依赖的转录。这些结果表明，Rb与一种谱系受限的ETS转录因子特异地相互作用。这种受调控的相互作用可能对于协调谱系特异性效应功能，如淋巴因子的产生和激活T细胞中的细胞周期进程可能是重要的。
The retinoblastoma gene product (Rb) is a nuclear phosphoprotein that regulates cell cycle progression. Elf-1 is a lymphoid-specific Ets transcription factor that regulates inducible gene expression during T cell activation. In this report, it is demonstrated that Elf-1 contains a sequence motif that is highly related to the Rb binding sites of several viral oncoproteins and binds to the pocket region of Rb both in vitro and in vivo. Elf-1 binds exclusively to the underphosphorylated form of Rb and fails to bind to Rb mutants derived from patients with retinoblastoma. Co-immunoprecipitation experiments demonstrated an association between Elf-1 and Rb in resting normal human T cells. After T cell activation, the phosphorylation of Rb results in the release of Elf-1, which is correlated temporally with the activation of Elf-1-mediated transcription. Overexpression of a phosphorylation-defective form of Rb inhibited Elf-1-dependent transcription during T cell activation. These results demonstrate that Rb interacts specifically with a lineage-restricted Ets transcription factor. This regulated interaction may be important for the coordination of lineage-specific effector functions such as lymphokine production with cell cycle progression in activated T cells.