Health / Medical Topics |
Pelp1 Estrogen Receptor Pathway
Proline-, glutamic acid-, leucine-rich protein 1 (Pelp1 or modulator of nongenomic activity of estrogen, MNAR) is a recently discovered transmitter of estrogen signals. The receptors for estrogen (ER), progestin (PR), androgen (AR) and others are steroid hormone receptors, which are part of a large family of ligand-inducible transcription factors. It has been established that estrogen has at least two courses of action termed classical or genomic and nongenomic. The classical activation cascade is well known. The nongenomic or nontranscriptional activation cascade for the estrogen receptor was determined based on the rapid response times observed for the activation of the MAPK cascade and other cell proliferation effects. The mechanism was believed to involve a membrane bound ER but attempts to isolate such a protein have not been successful. A second possibility would involve a scaffold protein that interacts with ER. Pelp1 appears to fit the second scenario. Pelp1 was first isolated as a coactivator of transcription for ER-alpha. It was observed that Pelp1 was expressed at levels 3-5 times normal in breast tumors. Several breast cancer cell lines have been shown to express Pelp1. Like many nuclear hormone receptors Pelp1 also interacts with Cbp and p300. More recently it has been demonstrated that Pelp1 mediates the interaction of ER and Src leading to the activation of the Mitogen Activated Protein Kinases Erk1 and Erk2. (NCI Thesaurus/BIOCARTA)