The LIM protein Ajuba recruits DBC1 and CBP/p300 to acetylate ERα and enhances ERα target gene expression in breast cancer cells.
Nucleic Acids Res
; 47(5): 2322-2335, 2019 03 18.
Article
in En
| MEDLINE
| ID: mdl-30597111
ABSTRACT
Estrogen/ERα signaling is critical for breast cancer progression and therapeutic treatments. Thus, identifying new regulators of this pathway will help to develop new therapeutics to overcome chemotherapy resistance of the breast cancer cells. Here, we report Ajuba directly interacts with ERα to potentiate ERα target gene expression, and biologically Ajuba promotes breast cancer cell growth and contributes to tamoxifen resistance of these cells. Ajuba constitutively binds the DBD and AF2 regions of ERα, and these interactions can be markedly enhanced by estrogen treatment. Mechanistically, Ajuba recruits DBC1 and CBP/p300 and forms a ternary complex to co-activate ERα transcriptional activity and concomitantly enhances ERα acetylation. Moreover, components of this complex can be found at endogenous promoters containing functional ERα responsive elements. Taken together, these data demonstrate that Ajuba functions as a novel co-activator of ERα and that Ajuba/DBC1/CBP/p300 ternary complex may be a new target for developing therapeutics to treat breast cancer.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Gene Expression Regulation, Neoplastic
/
Tumor Suppressor Proteins
/
Estrogen Receptor alpha
/
P300-CBP Transcription Factors
/
LIM Domain Proteins
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nucleic Acids Res
Year:
2019
Document type:
Article
Affiliation country:
China