Modulation of Runx2 activity by estrogen receptor-alpha: implications for osteoporosis and breast cancer.

ABSTRACT: The transcription factors Runx2 and estrogen receptor-alpha (ERalpha) are involved in numerous normal and disease processes, including postmenopausal osteoporosis and breast cancer. Using indirect immunofluorescence microscopy and pull-down techniques, we found them to colocalize and form complexes in a ligand-dependent manner. Estradiol-bound ERalpha strongly interacted with Runx2 directly through its DNA-binding domain and only indirectly through its N-terminal and ligand-binding domains. Runx2's amino acids 417-514, encompassing activation domain 3 and the nuclear matrix targeting sequence, were sufficient for interaction with ERalpha's DNA-binding domain. As a consequence of the interaction, Runx2's transcriptional activation activity was strongly repressed, as shown by reporter assays

SUBMITTER: Khalid O 

PROVIDER: S-EPMC2613062 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature