Rho GDP dissociation inhibitor α interacts with estrogen receptor α and influences estrogen responsiveness

Abstract

Estrogen receptor a (ERa) is a ligand-activated transcription factor that regulates expression of estrogen-responsive genes. Upon binding of the ligand-occupied ERa to estrogen response elements (EREs) in DNA, the receptor interacts with a variety of coregulatory proteins to modulate transcription of target genes. We have isolated and identified a number of proteins associated with the DNA-bound ERa. One of these proteins, Rho guanosine diphosphate (GDP) dissociation inhibitor a (RhoGDIa), is a negative regulator of the Rho family of GTP-binding proteins. In this study, we demonstrate that endogenously expressed RhoGDIa is present in the nucleus as well as the cytoplasm of MCF-7 breast cancer cells, and that RhoGDIa binds directly to ERa, alters the ERa-ERE interaction, and influences the ability of ERa to regulate transcription of a heterologous estrogen-responsive reporter plasmid in transient transfection assays as well as endogenous, estrogen-responsive genes in MCF-7 cells. Our studies suggest that, in addition to the activity of RhoGDIa in the cytoplasm, it also influences ERa signaling in the nucleus.

ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling

“…ARHGDIA partially colocalized with synaptopodin, which colocalizes with ARHGAP24 (31) and regulates RHOA signaling (Figure 2A) (32). ARHGDIA appeared to localize to the nucleus in some podocytes, and nuclear localization of ARHGDIA has been previously reported (33). ARHGDIA also colocalized with the phospholipase C ε 1 (PLCε1) protein, which is defective in SRNS type 3 (21).…”

Cancer/testis antigen SSX2 enhances invasiveness in MCF-7 cells by repressing ERα signaling

“…By comparing their peptide mass fingerprints to the IPI human database, eleven known proteins were identified and found to be a series of proteins related to proliferation, differentiation, apoptosis and cell survival (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). The SSX proteins are thought to act as transcriptional repressors through transcription repression domain (48).…”

“…ARHGDIA also known as Rho GDP dissociation inhibitor α, is a negative regulator of the RhoGTPase family (40). It has been previously described to interact with ERα and influence estrogen responsiveness (37). HSPB1 known as HSP27, interacts with ER and modulates ER function (41,50).…”

“Spot”-ting differences between the ectopic and eutopic endometrium of endometriosis patients

“…Considering that the formation of endometriotic lesions requires extensive cell invasion, these proteins appear to be well positioned for playing a modulatory role in the formation of endometriotic lesions. RhoGDIa is also known to bind directly to estrogen receptor a (ERa), altering the interaction of ERa with the estrogen response elements (44). Thus in endometriosis, an estrogen-dependant disorder, ectopic cells may be using Rho-GDIa to rewire the estrogen responsiveness.…”