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

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Cahill, Michael A
Jazayeri, Jalal A
Kovacevic, Zaklina
Richardson, Des R
Griffith University Author(s)
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2016
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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 nonstructured 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.

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Oncotarget

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7

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32

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© The Author(s) 2016. This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Oncology and carcinogenesis

Science & Technology

Life Sciences & Biomedicine

Cell Biology

signaling

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Cahill, MA; Jazayeri, JA; Kovacevic, Z; Richardson, DR, PGRMC1 regulation by phosphorylation: potential new insights in controlling biological activity, Oncotarget, 2016, 7 (32), pp. 50822-50827

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