Model-driven experimental approach reveals the complex regulatory distribution of p53 by the circadian factor Period 2
Abstract
Cells sense changes in environmental conditions and translate them into physiological responses that are mediated by a plethora of molecular intermediaries that converge at critical nodes. This is particularly relevant to multiple levels of biological organization in which the circadian clock and cell division are interlocked. Unexpectedly, the circadian rhythms of two critical components of the interlocked system, Period 2 (Per2) and p53, were in antiphase. This finding was analyzed using a systematic modeling approach, and predictions of the model were validated by experimental studies that revealed a distinct and complex scenario. Accordingly, we show that the spatiotemporal organization of Per2:p53 interactions and the nature of their chemical modifications are critical for their time-dependent subcellular redistribution and potential biological functions.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- November 2016
- DOI:
- 10.1073/pnas.1607984113
- Bibcode:
- 2016PNAS..11313516G