PGRMC1 regulation by phosphorylation: potential new insights in controlling biological activity

Oncotarget
M A CahillDes R Richardson

Abstract

Progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein implicated in multiple pathologies, including cancer and Alzheimer's disease. The recently published structure of PGRMC1 revealed heme-mediated dimerization that directed the PGRMC1-dependent cytochrome P450-mediated detoxification of doxorubicin. We describe here how the PGRMC1 structure also enables important new insights into the possible regulation of PGRMC1 function by phosphorylation. Predicted regulatory interaction sites for SH2- and SH3-domain proteins are in non-structured regions that could be available to cytoplasmic enzymes. Further to the published interpretation, we suggest that phosphorylation of PGRMC1 at position Y113 may promote the attested membrane trafficking function of PGRMC1. To stimulate further experimentation, we also discuss that heme-mediated dimerization of PGRMC1 and membrane trafficking may be mutually exclusive functions. These roles could potentially be reciprocally regulated by phosphorylation/dephosphorylation at Y113. It follows that the phosphorylation status of PGRMC1 should be further explored in order to better understand many of its proposed biological functions.

References

Mar 13, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Flavio Meggio, Lorenzo A Pinna
Oct 16, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Erik Runko, Zaven Kaprielian
Mar 25, 2006·Nature Reviews. Cancer·Arne OstmanFrank D Böhmer
Nov 23, 2006·Molecular & Cellular Proteomics : MCP·Richard P MuntonIsabelle M Mansuy
May 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kwang-Il GohAlbert-László Barabási
Jun 23, 2007·The Journal of Steroid Biochemistry and Molecular Biology·Michael A Cahill
Feb 19, 2010·The Journal of Pharmacology and Experimental Therapeutics·Ikhlas S AhmedRolf J Craven
Feb 2, 2012·Expert Opinion on Drug Metabolism & Toxicology·Ikhlas S A AhmedRolf J Craven
Jan 17, 2015·Oncoscience·Kaia K Hampton, Rolf J Craven

❮ Previous
Next ❯

Citations

Mar 3, 2017·Bioscience Trends·Michael A Cahill
Apr 5, 2020·BMC Molecular and Cell Biology·Bashar M ThejerMichael A Cahill
Apr 12, 2020·Molecular Phylogenetics and Evolution·Elisabeth HehenbergerMichael A Cahill
Jul 10, 2020·Cell·Mehdi BouhaddouNevan J Krogan
Jan 26, 2020·Biochemical and Biophysical Research Communications·Sarah L TeakelMichael A Cahill

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR

Software Mentioned

JSmol Viewer

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.