Protein complexes including PGRMC1 and actin-associated proteins are disrupted by AG-205

Biochem Biophys Res Commun. 2020 Mar 26;524(1):64-69. doi: 10.1016/j.bbrc.2019.12.108. Epub 2020 Jan 21.

Abstract

PGRMC1 is a protein from the MAPR family with a range of cellular functions. PGRMC1 has been described to play a role in fertility, neuroprotection, steroidogenesis, membrane trafficking and in cancer cell biology. PGRMC1 represents a likely key regulator of cell metabolism and proliferation, as well as a potential target for anti-cancer therapies. To further understand the functions of PGRMC1 and the mechanism of the small molecule inhibitor of PGRMC1, AG-205, proteins differentially bound to PGRMC1 were identified following AG-205 treatment of MIA PaCa-2 cells. Our results suggest that AG-205 influences PGRMC1 interactions with the actin cytoskeleton. The binding of two PGRMC1-associated proteins that support this, RACK1 and alpha-Actinin-1, was reduced following AG-205 treatment. The biology associated with PGRMC1 binding partners identified here merits further investigation.

Keywords: Actin cytoskeleton; Affinity proteomics; Cytochrome b5 domain; MAPR; Membrane trafficking; Membrane-associated progesterone receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism*
  • Cell Line, Tumor
  • Humans
  • Indoles / metabolism*
  • Mass Spectrometry
  • Membrane Proteins / antagonists & inhibitors*
  • Protein Binding
  • Receptors for Activated C Kinase / metabolism
  • Receptors, Progesterone / antagonists & inhibitors*

Substances

  • AG 205
  • Actins
  • Indoles
  • Membrane Proteins
  • PGRMC1 protein, human
  • Receptors for Activated C Kinase
  • Receptors, Progesterone