| First Author | Devos J | Year | 2011 |
| Journal | J Circadian Rhythms | Volume | 9 |
| Issue | 1 | Pages | 12 |
| PubMed ID | 22208286 | Mgi Jnum | J:215866 |
| Mgi Id | MGI:5607219 | Doi | 10.1186/1740-3391-9-12 |
| Citation | Devos J, et al. (2011) Magel2, a Prader-Willi syndrome candidate gene, modulates the activities of circadian rhythm proteins in cultured cells. J Circadian Rhythms 9(1):12 |
| abstractText | BACKGROUND: The Magel2 gene is most highly expressed in the suprachiasmatic nucleus of the hypothalamus, where its expression cycles in a circadian pattern comparable to that of clock-controlled genes. Mice lacking the Magel2 gene have hypothalamic dysfunction, including circadian defects that include reduced and fragmented total activity, excessive activity during the subjective day, but they have a normal circadian period. Magel2 is a member of the MAGE family of proteins that have various roles in cellular function, but the specific function of Magel2 is unknown. METHODS: We used a variety of cell-based assays to determine whether Magel2 modifies the properties of core circadian rhythm proteins. RESULTS: Magel2 represses the activity of the Clock:Bmal1 heterodimer in a Per2-luciferase assay. Magel2 interacts with Bmal1 and with Per2 as measured by co-immunoprecipitation in co-transfected cells, and exhibits a subcellular distribution consistent with these interactions when visualized by immunofluorescence. As well, Magel2 induces the redistribution of the subcellular localization of Clock towards the cytoplasm, in contrast to the nucleus-directed effect of Bmal1 on Clock subcellular localization. CONCLUSION: Consistent with the blunted circadian rhythm observed in Magel2-null mice, these data suggest that Magel2 normally promotes negative feedback regulation of the cellular circadian cycle, through interactions with key core circadian rhythm proteins. |
