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Publication : GPR50 interacts with TIP60 to modulate glucocorticoid receptor signalling.

First Author  Li J Year  2011
Journal  PLoS One Volume  6
Issue  8 Pages  e23725
PubMed ID  21858214 Mgi Jnum  J:176354
Mgi Id  MGI:5291531 Doi  10.1371/journal.pone.0023725
Citation  Li J, et al. (2011) GPR50 interacts with TIP60 to modulate glucocorticoid receptor signalling. PLoS One 6(8):e23725
abstractText  GPR50 is an orphan G-protein coupled receptor most closely related to the melatonin receptors. The physiological function of GPR50 remains unclear, although our previous studies implicate the receptor in energy homeostasis. Here, we reveal a role for GPR50 as a signalling partner and modulator of the transcriptional co-activator TIP60. This interaction was identified in a yeast-two-hybrid screen, and confirmed by co-immunoprecipitation and co-localisation of TIP60 and GPR50 in HEK293 cells. Co-expression with TIP60 increased perinuclear localisation of full length GPR50, and resulted in nuclear translocation of the cytoplasmic tail of the receptor, suggesting a functional interaction of the two proteins. We further demonstrate that GPR50 can enhance TIP60-coactiavtion of glucocorticoid receptor (GR) signalling. In line with in vitro results, repression of pituitary Pomc expression, and induction of gluconeogenic genes in liver in response to the GR agonist, dexamethasone was attenuated in Gpr50(-/-) mice. These results identify a novel role for GPR50 in glucocorticoid receptor signalling through interaction with TIP60.
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