The emerging role of progesterone receptor membrane component 1 (PGRMC1) in cancer biology

Michael A. Cahill, Jalal A. Jazayeri, Susan M. Catalano, Shinya Toyokuni, Zaklina Kovacevic, Des R. Richardson

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)


Progesterone receptor membrane component 1 (PGRMC1) is a multi-functional protein with a heme-binding moiety related to that of cytochrome b5, which is a putative progesterone receptor. The recently solved PGRMC1 structure revealed that heme-binding involves coordination by a tyrosinate ion at Y113, and induces dimerization which is stabilized by hydrophobic stacking of heme on adjacent monomers. Dimerization is required for association with cytochrome P450 (cyP450) enzymes, which mediates chemoresistance to doxorubicin and may be responsible for PGRMC1's anti-apoptotic activity. Here we review the multiple attested involvement of PGRMC1 in diverse functions, including regulation of cytochrome P450, steroidogenesis, vesicle trafficking, progesterone signaling and mitotic spindle and cell cycle regulation. Its wide range of biological functions is attested to particularly by its emerging association with cancer and progesterone-responsive female reproductive tissues. PGRMC1 exhibits all the hallmarks of a higher order nexus signal integration hub protein. It appears capable of acting as a detector that integrates information from kinase/phosphatase pathways with heme and CO levels and probably redox status.
Original languageEnglish
Pages (from-to)339-349
Number of pages11
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Issue number2
Publication statusPublished - 2016


Dive into the research topics of 'The emerging role of progesterone receptor membrane component 1 (PGRMC1) in cancer biology'. Together they form a unique fingerprint.

Cite this