Molecular cloning and characterization of PELP1, a novel human coregulatorof estrogen receptor alpha

Nuclear hormone receptors (NRs) are transcription factors whose activity is regulated by ligands and by coactivators or corepressors. We report the ch aracterization of a new NR coregulator: proline-, glutamic acid-, leucine-r ich protein 1 (PELP1), a novel human protein that comprises 1,282 amino aci ds and is localized on chromosome 17. The primary structure of PELP1 consis ts of several motifs present in most transcriptional regulators including n ine NR-interacting boxes (LXXLL motifs), a zinc finger, and glutamic acid- and proline-rich regions. We demonstrate that PELP1 is a coactivator of est rogen receptor alpha (ER alpha). PELP1 enhances 17 beta -estradiol-dependen t transcriptional activation from the estrogen response element in a dose-d ependent manner. PELP1 interacts with ER alpha and also with general transc riptional coactivators p300 and cAMP response element-binding protein-bindi ng protein. PELP1 was differentially expressed in various human and murine tissues with the highest expression levels in the testes, mammary glands, a nd brain. We also provide evidence supporting the developmental regulation of PELP1 expression in murine mammary glands, the detectable expression of PELP1 in human mammary cancer cell lines, and the enhanced expression of PE LP1 in human breast tumors. These findings suggest that PELP1 is a novel co regulator of ER alpha and may have a role in breast cancer tumorigenesis.