Reactome | GREB1 binds ESR1:ESTG and co-activators

GREB1 binds ESR1:ESTG and co-activators

Stable Identifier

R-HSA-9038052

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

In addition to being an estrogen-responsive target, GREB1 also interacts directly with ESR1 and functions as an coactivator at numerous estrogen-responsive promoters, as assessed in MCF7 cell lines, xenograft models and primary tumors (Mohammed et al, 2013). ESR1-binding coincides with ~95% of GREB1 binding events sites as assessed by ChIP-seq, and expression of up to half of ESR1- and estrogen-dependent genes is compromised when GREB1 expression is silenced, without affecting ESR1 binding. GREB1 may function to stabilize interactions with other coactivators such as EP300 and CREBBP (also known as p300 and CBP, respectively), as co-occupancy with these proteins is lost upon GREB1 silencing (Mohammed et al, 2013). GREB1 expression is high in ER+ cancers and is associated with positive prognosis (Mohammed et al, 2013; reviewed in Hodgkinson and Vanderhyden, 2014).

Literature References

PubMed ID	Title	Journal	Year
24998469	Consideration of GREB1 as a potential therapeutic target for hormone-responsive or endocrine-resistant cancers Hodgkinson, KM, Vanderhyden, BC	Expert Opin. Ther. Targets	2014
23403292	Endogenous purification reveals GREB1 as a key estrogen receptor regulatory factor Ross-Innes, CS, D'Santos, C, Saadi, A, Palmieri, C, Mohammed, H, Atkins, A, Rueda, OM, Chin, SF, Serandour, AA, Holmes, KA, Ali, HR, Robinson, JL, Zwart, W, Stingl, J, Caldas, C, Brown, GD, Menon, S, Carroll, JS, Theodorou, V	Cell Rep	2013