کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2030017 | 1071013 | 2008 | 10 صفحه PDF | دانلود رایگان |
SummaryFoxO transcription factors regulate the transcription of genes that control metabolism, cellular proliferation, stress tolerance, and possibly life span. A number of posttranslational modifications within the forkhead DNA-binding domain regulate FoxO-mediated transcription. We describe the crystal structures of FoxO1 bound to three different DNA elements and measure the change in FoxO1-DNA affinity with acetylation and phosphorylation. The structures reveal additional contacts and increased DNA distortion for the highest affinity DNA site. The flexible wing 2 region of the forkhead domain was not observed in the structures but is necessary for DNA binding, and we show that p300 acetylation in wing 2 reduces DNA affinity. We also show that MST1 phosphorylation of FoxO1 prevents high-affinity DNA binding. The observation that FoxO-DNA affinity varies between response elements and with posttranslational modifications suggests that modulation of FoxO-DNA affinity is an important component of FoxO regulation in health and misregulation in disease.
Journal: - Volume 16, Issue 9, 10 September 2008, Pages 1407–1416