Identification and function of coactivator of estrogen receptor: ERIAP
- 9 Downloads
Estrogen receptor (ER), one member of nuclear hormone receptor (NR) family, is an estrogen-dependent transcriptional factor that plays an important role in development, progression and treatment of breast cancer. Transcriptional co-factors (co-activators and co-repressors) are critical for ER to transduce hormone and metabolic signaling to target genes. A number of functional and structural studies have elucidated the precise mechanisms of co-activator interaction with the ligand-inducible activation domain in ER via one and several LXXLL motifs (where X is any amino acid) known as NR-Box. By the yeast two-hybrid system we have identified a novel ER-α interacting protein ERIAP (Estrogen Receptor Interacting and Activating Protein) which contains two consensus LXXLL motifs. ERIAP associated with ER-α in a ligand-dependent manner, as demonstrated by in vivo immunoprecipitation and in vitro GST capture assays. The two NR boxes were essential for ERIAP interaction with ER-α. Furthermore, ERIAP specifically enhanced ligand-mediated ER-α transcriptional activity in a dose-dependent fasion and increased the expression of estrogen-responsive gene pS2. Thus, our present findings indicate that ERIAP funcions as a new coactivator for ER-α transcriptional activity, which may play an important role in development and progression of breast cancer.
Keywordsestrogen receptor breast cancer new gene ERIAP
- 5.Russo, J., Hu, Y. F., Yang, X. et al., Developmental, cellular, and molecular basis of human breast cancer, J. Natl. Cancer Inst., 2000, 27: 17–37.Google Scholar
- 21.Wong, C. W., Komm, B., Cheskis, B. J., Structure-function evaluation of ER alpha and beta interplay with SRC family coactivators, ER selective ligands, Biochemistry, 2001, 40: 6756–6765.Google Scholar