Pelp1ModulationofEstrogenReceptorActivity

Proline-,glutamic acid-,leucine-rich protein 1 (Pelp1 also known as:modulator of nongenomic activity of estrogen or 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 and an example of this is illustrated in the Carm1 pathway. 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 by Vadlamudi et al as a coactivator of transcription for ER-alpha. They 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. Vadlamudi et al also showed that like many nuclear hormone receptors Pelp1 also interacts with Cbp and p300. More recently Wong et al. demonstrated that Pelp1 mediates the interaction of ER and Src leading to the activation of the Mitogen Aactivated Protein Kinases Erk1 and Erk2.

Contributor: Roger Anderson Ph.D.

REFERENCES: Vadlamudi RK, Wang RA, Mazumdar A, Kim Y, Shin J, Sahin A, Kumar R. Molecular cloning and characterization of PELP1, a novel human coregulator of estrogen receptor alpha. J Biol Chem. 2001 Oct 12;276(41):38272-9. Wong CW, McNally C, Nickbarg E, Komm BS, Cheskis BJ. Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14783-8.