XB-ART-6793
J Biol Chem
2002 Oct 04;27740:37037-44. doi: 10.1074/jbc.M111607200.
Show Gene links
Show Anatomy links
Regulation of GRIP1 and CBP Coactivator activity by Rho GDI modulates estrogen receptor transcriptional enhancement.
???displayArticle.abstract???
Estrogen receptor alpha (ER) coordinates gene expression with cellular physiology in part by controlling receptor- cofactor interactions in response to extracellular signals. We have previously shown that the Rho signaling pathway modulates ER transcriptional activation. We now demonstrate that Rho GDI-dependent increase in ER transactivation is dependent on the ER AF-2 coactivator binding site, prompting us to examine regulation of receptor coactivators by Rho GDI. Indeed, Rho GDI cooperates with GRIP1 to increase ER ligand-independent and ligand-dependent transactivation and also enhances GRIP1 transcriptional activity when GRIP1 is tethered to DNA. The GRIP1 activation domain 1 (AD1), which binds CBP/p300, is necessary for Rho GDI to modulate GRIP1 activity. Using E1A to inhibit the endogenous CBP/p300 and a Gal4-CBP fusion protein to assay CBP activity, we find that the effect of Rho GDI on ER transactivation is CBP/p300-dependent. Importantly, the ability of CBP/p300 to transduce the Rho GDI signal to ER occurs through both GRIP1-dependent and -independent pathways. These data suggest a complex interplay between ER transcriptional activation and the Rho signaling pathways through modulation of receptor cofactors, which may have evolved to coordinate receptor-dependent gene expression with Rho-regulated events, such as cell migration. We speculate that dysregulation of the Rho-ER axis may participate in cancer progression.
???displayArticle.pubmedLink??? 12138084
???displayArticle.link??? J Biol Chem
???displayArticle.grants???
Species referenced: Xenopus
Genes referenced: crebbp ep300 grip1 lgals12 lgals4.2 mst1 ncoa2 rho rho.2