PML regulates PER2 nuclear localization and circadian function
| Autor: | Miki, Takao, Xu, Zhixiang, Chen-Goodspeed, Misty, Liu, Mingguang, Van Oort-Jansen, Anita, Rea, Michael A, Zhao, Zhaoyang, Lee, Cheng Chi, Chang, Kun-Sang |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Cell Nucleus
Male endocrine system Cytoplasm Transcription Genetic Tumor Suppressor Proteins CLOCK Proteins Nuclear Proteins Acetylation Period Circadian Proteins Fibroblasts Promyelocytic Leukemia Protein Article Cell Line Circadian Rhythm Mice Sirtuin 1 Circadian Clocks Animals Suprachiasmatic Nucleus Transcription Factors |
| Popis: | Studies have suggested that the clock regulator PER2 is a tumour suppressor. A cancer network involving PER2 raises the possibility that some tumour suppressors are directly involved in the mammalian clock. Here, we show that the tumour suppressor promyelocytic leukaemia (PML) protein is a circadian clock regulator and can physically interact with PER2. In the suprachiasmatic nucleus (SCN), PML expression and PML-PER2 interaction are under clock control. Loss of PML disrupts and dampens the expression of clock regulators Per2, Per1, Cry1, Bmal1 and Npas2. In the presence of PML and PER2, BMAL1/CLOCK-mediated transcription is enhanced. In Pml(-/-) SCN and mouse embryo fibroblast cells, the cellular distribution of PER2 is primarily perinuclear/cytoplasmic. PML is acetylated at K487 and its deacetylation by SIRT1 promotes PML control of PER2 nuclear localization. The circadian period of Pml(-/-) mice displays reduced precision and stability consistent with PML having a role in the mammalian clock mechanism. |
| Databáze: | OpenAIRE |
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