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首页> 外文期刊>Molecular and Cellular Biology >Differential Regulation of E2F1, DP1, and the E2F1/DP1 Complex by ARF
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Differential Regulation of E2F1, DP1, and the E2F1/DP1 Complex by ARF

机译：ARF对E2F1，DP1和E2F1 / DP1复合物的差异调节

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The tumor suppressor protein ARF inhibits MDM2 to activate and stabilize p53. Recent studies provided evidence for p53-independent tumor suppression functions of ARF. For example, it has been shown that ARF induces proteolysis of certain E2F species, including E2F1. In addition, ARF relocalizes E2F1 from the nucleoplasm to nucleolus and inhibits E2F1-activated transcription. Because DP1 is a functional partner of the E2F family of factors, we investigated whether DP1 is also regulated by ARF. Here we show that DP1 associates with ARF. Coexpression of ARF relocalizes DP1 from the cytoplasm to the nucleolus, suggesting that DP1 is also a target of the ARF regulatory pathways. Surprisingly, however, the E2F1/DP1 complex is refractory to ARF regulation. Coexpression of E2F1 and DP1 blocks ARF-induced relocalization of either subunit to the nucleolus. The E2F1/DP1 complex localizes in the nucleoplasm, whereas ARF is detected in the nucleolus, suggesting that ARF does not interact with the E2F1/DP1 complex. Moreover, we show that E2F1 is more stable in the presence of ARF when coexpressed with DP1. These results suggest that ARF differentially regulates the free and heterodimeric forms of E2F1 and DP1. DP1 is a constitutively expressed protein, whereas E2F1 is mainly expressed at the G1/S boundary of the cell cycle. Therefore, the E2F1/DP1 complex is abundant only between late G1 and early S phase. Our results on the differential regulation E2F1, DP1, and the E2F1/DP1 complex suggest the possibility that ARF regulates the function of these cell cycle factors by altering the dynamics of their heterodimerization during progression from G1 to S phase.
机译：肿瘤抑制蛋白ARF抑制MDM2激活并稳定p53。最近的研究为ARF不依赖p53的肿瘤抑制功能提供了证据。例如，已经显示ARF诱导某些E2F种类包括E2F1的蛋白水解。此外，ARF将E2F1从核质重新定位到核仁，并抑制E2F1激活的转录。由于DP1是E2F因子家族的功能伙伴，因此我们研究了DP1是否也受ARF调节。在这里，我们显示DP1与ARF相关联。 ARF的共表达将DP1从细胞质重新定位到核仁，表明DP1也是ARF调节途径的靶标。然而，令人惊讶的是，E2F1 / DP1复合物对ARF调节是难治的。 E2F1和DP1的共表达可阻止ARF诱导的任一亚基向核仁的重新定位。 E2F1 / DP1复合物位于核质中，而在核仁中检测到ARF，这表明ARF不与E2F1 / DP1复合物相互作用。此外，我们显示当与DP1共表达时，在ARF存在下E2F1更稳定。这些结果表明，ARF差异调节E2F1和DP1的游离和异二聚体形式。 DP1是组成型表达的蛋白质，而E2F1主要在细胞周期的G 1 / S边界表达。因此，E2F1 / DP1复合体仅在G 1 晚期和S早期之间富集。我们对差异调节E2F1，DP1和E2F1 / DP1复合物的研究结果表明，ARF可能通过改变从G 1 到S的异源二聚化动力学来调节这些细胞周期因子的功能。相。

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