Disease relevance of PGRMC1

• This result is mirrored by effects of an antibody raised against the recombinant E. coli mPR which suppressed the rapid progesterone-initiated Ca2+ increase in sperm [1].
• We report here that the Hpr6.6 protein regulates the response to oxidative damage in breast cancer cells [2].
• After the start of the nationwide measles, parotitis, and rubella (MPR) vaccination programme in 1982 in Finland, encephalitides associated with these viruses seem to have totally vanished [3].
• Addition of the antibodies to the medium of Morris hepatoma 7777 cells, which express only the Mr 46,000 MPR, resulted in a decreased intracellular retention and increased secretion of newly synthesized lysosomal enzymes [4].
• At follow-up, a steeper correlation was found between MPR and minimal stenosis diameter (MPR1: slope, 0.52 versus 0.91; MPR2: slope, 1.48 versus 1.95) and between MaxFR and net lumen gain (slope, 0.78 versus 1.27) [5].
• PGRMC1's role in regulating the viability of ovarian cancers was assessed by overexpressing PGRMC1, depleting PGRMC1 using small interfering RNA, and attenuating PGRMC1's action with a blocking antibody [6].

High impact information on PGRMC1

• TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo [7].
• These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi [7].
• TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway [7].
• Second, we examine the physiological and biochemical data supporting the concept of cognate membrane receptors for P, E, and T, the so-called mPR, mER, and mTR [8].
• fEndosome-to-Golgi retrieval of the mannose 6-phosphate receptor (MPR) is required for lysosome biogenesis [9].

Chemical compound and disease context of PGRMC1

• Adherence to statin therapy, as reflected by MPR, is closely related to LDL cholesterol goal attainment in patients with diabetes and dyslipidemia [10].
• We have previously shown that the insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-II/MPR) exhibits a polarized cell surface distribution in the human colon adenocarcinoma (Caco-2) cell line in which there is a threefold enrichment on the basolateral surface [11].
• Moreover, in breast cancer cells MCF-7 dioxin induced mPR expression [12].
• A decrease in the amount of 5-HT released by projections from the MPR to the trigeminal nucleus could be partially responsible for the pain experienced in migraine headache [13].

Biological context of PGRMC1

• Applying this technology to membrane protein complexes, we discovered a previously unknown direct interaction of the progesterone-binding membrane protein PGRMC1 with Insig-1, a key regulator of cholesterol homeostasis [14].
• Immunoprecipitation with the PAIRBP1 antibody pulled down the membrane P4 binding protein known as progesterone receptor membrane complex-1 (PGRMC1; rat homolog accession number AJ005837) [15].
• Hpr6.6 protein mediates cell death from oxidative damage in MCF-7 human breast cancer cells [2].
• Hpr6.6 is located on the X chromosome and dg6 on chromosome 4 [16].
• Antibodies that block the ligand binding site of the cation-dependent mannose 6-phosphate specific receptor (Mr 46,000 MPR) were used to probe the function of the receptor in transport of lysosomal enzymes [4].

Anatomical context of PGRMC1

• PGRMC1 and its binding partner, plasminogen activator inhibitor RNA-binding protein-1 (PAIRBP1), were detected in human granulosa/luteal cells [17].
• Here we show that expression of mPR-cDNA in CHO cells leads to increased microsomal progesterone binding [1].
• In control fibroblasts that express both types of MPR, the secretion-recapture pathway is of minor importance [18].
• MPR and lysosomal enzymes were also found in coated pits of the plasma membrane [19].
• On this basis, it has been proposed that cells lacking MPR are poor targets for cytotoxic lymphocytes that mediate allograft rejection or tumor immune surveillance [20].

Associations of PGRMC1 with chemical compounds

• Our results support the assumption that mPR represents the first steroid membrane receptor or a part of it involved in rapid, nongenomic steroid signalling [1].
• Baf did not interfere with transport of HRP to MPR-labeled late endosomes, but nearly completely abrogated transport to cathepsin D-labeled lysosomes [21].
• When the cells were treated with the lysosomotropic amine primaquine, binding of anti-MPR to the cells in culture was reduced by half [19].
• In a second approach, sections of formalin-fixed breast biopsy specimens were probed with biotinylated MPR [22].
• The phosphorylated MPR 300-CT was cross-linked by means of bis(sulfosuccinimidyl)suberate mainly to a cytosolic protein of 35 kDa (referred to as TIP 35) and to 35- and 91-kDa proteins salt-washed from bovine brain membranes [23].

Other interactions of PGRMC1

• In this context, a putative progesterone membrane binding protein (mPR) has been identified, recently [1].
• Objective: Our objective was to assess the role of the nuclear P4 receptor (PGR) and PGR membrane component 1 (PGRMC1) in mediating P4's antiapoptotic action in human granulosa/luteal cells [17].

Analytical, diagnostic and therapeutic context of PGRMC1

• Immunocytochemistry showed that MPR accumulated in TGR, especially in coated buds [19].
• In one approach, extracts of frozen tissue were standardized to protein content, fractionated by SDS-PAGE, immobilized on nitrocellulose, and probed with iodinated MPR [22].
• Man-6-P glycoproteins were also isolated from rat brain by MPR affinity chromatography on a preparative scale [24].
• Using iodinated cation independent MPR as a probe in a Western blot assay, we surveyed levels of Man-6-P glycoproteins in a number of different rat tissues [24].
• We examined the expression of MPR on the cell surface of a panel of 43 myelomonocytic, erythroid and megakaryocytic leukemia cell lines and 21 primary acute myeloid leukemia (AML) cases by flow cytometry [25].

References