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Mechanisms of transcriptional regulation by Rb-E2F segregate by biological pathway

Abstract

The E2F family of transcription factors are critical regulators of the cell cycle and have also been implicated in apoptosis, development, DNA damage checkpoints, and differentiation. Retinoblastoma (Rb) proteins interact with E2F to regulate transcription, and several mechanisms have been proposed for Rb-E2F transcriptional regulation. We designed microarray-based experiments to characterize the relative contributions of each mechanism, and unexpectedly, we found that distinct functional gene groups show preference for one mechanism over the others. We propose that such a distribution may provide signaling specificity to enable regulatory proteins to turn on or off entire pathways that determine cell fate.

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Acknowledgements

We thank Mark Watson, Kate Hamilton, and Laura Voss for their help and advice on microarrays, and Douglas Dean for intellectual contribution and support in the early stages of this work. This work was supported by grants from the National Institutes of Health (CA 85839) and the American Heart Association (EI9940116N) to GDL.

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Correspondence to Gregory D Longmore.

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Young, A., Nagarajan, R. & Longmore, G. Mechanisms of transcriptional regulation by Rb-E2F segregate by biological pathway. Oncogene 22, 7209–7217 (2003). https://doi.org/10.1038/sj.onc.1206804

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