Hormone signaling is important in a number of disease states, and hormone receptors are effective therapeutic targets. PGRMC1 (progesterone receptor membrane component 1) is a member of a multi-protein complex that binds to progesterone and other steroids, as well as pharmaceutical compounds. In spite of its name, PGRMC1 shares homology with cytochrome b5-related proteins rather than hormone receptors, and heme binding is the sole biochemical activity of PGRMC1. PGRMC1 and its homologues regulate cholesterol synthesis by activating the P450 protein Cyp51/lanosterol demethylase, and the cholesterol synthetic pathway is an important target in cardiovascular disease and in treating infections. PGRMC1 binding partners include multiple P450 proteins, PAIR-BP1, Insig, and an uncharacterized hormone/drug-binding protein. PGRMC1 is induced in a spectrum of cancers, where it promotes cell survival and damage resistance, and PGRMC1 is also expressed in the nervous system and tissues involved in drug metabolism, cholesterol synthesis and hormone synthesis and turnover. One of the appealing features of PGRMC1 and its associated protein complex is its affinity for steroids and drugs. Together with its biological role in promoting tumor survival, PGRMC1 is an attractive target for therapeutic intervention in cancer and related malignancies.
|Number of pages||6|
|Journal||Pharmacology and Therapeutics|
|State||Published - Jan 2009|
Bibliographical noteFunding Information:
We are grateful to Clay Adams Condley and Martin Bard for helpful discussions about PGRMC1. This work was supported in part by the American Cancer Society, grant number 85-001-19-IRG, the NIH grant COBRE P20 RR 15592 and BIRCWH (Building Interdisciplinary Research Careers in Women's Health) grant K12DA 14040-06.
- P450 proteins
ASJC Scopus subject areas
- Pharmacology (medical)