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• W2156836899 endingPage "8408" @default.
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• W2156836899 abstract "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." @default.
• W2156836899 created "2016-06-24" @default.
• W2156836899 creator A5029856778 @default.
• W2156836899 creator A5079077636 @default.
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• W2156836899 date "2002-12-01" @default.
• W2156836899 modified "2023-09-24" @default.
• W2156836899 title "Differential Regulation of E2F1, DP1, and the E2F1/DP1 Complex by ARF" @default.
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• W2156836899 doi "https://doi.org/10.1128/mcb.22.24.8398-8408.2002" @default.
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