Disease relevance of PLRG1

• The prl1 mutation localized by T-DNA tagging on Arabidopsis chromosome 4-44 confers hypersensitivity to glucose and sucrose [1].
• We stably transfected human A549 lung cancer cells with several short hairpin RNAs for PRL-1 and found decreased invasive activity in the resulting clones compared with control cells [2].
• The present study was undertaken to test the ability of 16K hPRL to inhibit the growth of human HCT116 colon cancer cells transplanted s.c. into Rag1(-/-) mice [3].
• These findings support the potential of 16K hPRL as a therapeutic agent for the treatment of colorectal cancer [3].
• These results support the hypothesis that PRL-1 plays an important role in maintaining the malignant phenotype by exploiting Src activation processes, and that PRL-1 could be a promising therapeutic target for cancer metastasis and cell growth [2].

High impact information on PLRG1

• Crystal structures of SarA, a pleiotropic regulator of virulence genes in S. aureus [4].
• The prl1 mutation also augments the sensitivity of plants to growth hormones including cytokinin, ethylene, abscisic acid, and auxin; stimulates the accumulation of sugars and starch in leaves; and inhibits root elongation [1].
• Potential functional conservation of PRL1 homologs found in other eukaryotes is indicated by nuclear localization of PRL1 in monkey COS-1 cells and selective interaction of PRL1 with a nuclear protein kinase C-betaII isoenzyme involved in human insulin signaling [1].
• NF-kappa B is a pleiotropic regulator of a variety of genes implicated in the cellular response to injury [5].
• In this study, we evaluated the role of PRL-1 in cell proliferation and metastatic processes in human lung cancer cells [2].

Chemical compound and disease context of PLRG1

• PRL-1 tyrosine phosphatase regulates c-Src levels, adherence, and invasion in human lung cancer cells [2].
• In this study, we evaluated the effect of halofuginone on PRL-1 expression, its cellular localization in vitro and during liver regeneration, and fibrosis progression in vivo [6].
• Radioimmunoassayable basal serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (hPRL), 17 beta-estradiol (E2) and testosterone (T) were estimated in a total of 68 patients, who were treated because of peptic ulcer with 1 g cimetidine per day [7].
• Luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (hPRL) and testosterone (T) were assayed in a total of 131 patients with peptic ulcer [8].

Biological context of PLRG1

• In immunofluorescence studies, reduction in PRL-1 seemed to decrease cell membrane protrusions with a reduction in actin fiber extensions in spite of continuous phosphorylation of Tyr397 FAK, which could reflect reduced adhesion turnover [2].
• Mitogenic up-regulation of the PRL-1 protein-tyrosine phosphatase gene by Egr-1. Egr-1 activation is an early event in liver regeneration [9].
• Gene expression of the liver indicated reduced expression of small heterodimer partner, a pleiotropic regulator of diverse metabolic pathways, as well as genes for both fatty acid synthesis and gluconeogenesis, by treatment with colestimide [10].
• Inhibition of NF-kappaB activation by overexpression of a nondegradable inhibitor kappaB-alpha mutant or treatment with NF-kappaB inhibitors blocked 16K hPRL-induced apoptosis [11].
• Restriction enzyme analysis of the hPRL gene with methylation-sensitive endonucleases disclosed no correlation between the extent of methylation and gene activity for ThaI, AvaI, and HhaI recognition sequences [12].

Anatomical context of PLRG1

• The human proteins CDC5L (hCDC5) and PLRG1 are both highly conserved components of a multiprotein complex that is a subunit of the spliceosome [13].
• The M(r) 16,000 NH(2)-terminal fragment of human prolactin (16K hPRL) is a potent antiangiogenic factor inhibiting endothelial cell function in vitro and neovascularization in vivo [3].
• From the human B-lymphoblastoid cell line IM-9-P, we derived the IM-9-P series of clonal sublines that differ from each other in the degree of human PRL (hPRL) production [12].
• Here, we examined whether the nuclear factor-kappaB (NF-kappaB) signaling pathway was involved in mediating the apoptotic action of 16K hPRL in bovine adrenal cortex capillary endothelial cells [11].
• Treatment with recombinant 16K hPRL increased DNA fragmentation in cultured bovine brain capillary endothelial (BBE) and human umbilical vein endothelial (HUVE) cells in a time- and dose-dependent fashion, independent of the serum concentration [14].

Associations of PLRG1 with chemical compounds

• The prl1 mutation results in transcriptional derepression of glucose responsive genes defining a novel suppressor function in glucose signaling [1].
• Total tyrosine FAK phosphorylation and Tyr397 phosphorylation levels were continuously elevated in PRL-1 knockdown cells plated on fibronectin [2].
• Furthermore, using the complete hPRL upstream region, we show that estrogen induction is abolished by simultaneous thyroid hormone treatment [15].
• In this report we show that thyroid hormone inhibits the expression of the hPRL gene in rat pituitary cells [15].
• Exposure of the cells to the nucleoside 1-beta-D-arabinofuranosylcytosine, which has been reported to increase enzymatic DNA-methylation, led to an elevation of hPRL production that persisted after removal of the drug [12].

Other interactions of PLRG1

• A direct interaction between the carboxyl-terminal region of CDC5L and the WD40 domain of PLRG1 is essential for pre-mRNA splicing [13].
• INTRODUCTION: Interleukin-6 (IL-6) is a pleiotropic regulator of prostate cancer cell growth [16].
• Although TSP-1 can act as a pleiotropic regulator for human vascular smooth muscle cells (HVSMCs), the intracellular signaling pathways stimulated by this protein remain obscure [17].
• BACKGROUNDS: Infection by virus or treatment with double-stranded RNA (dsRNA) results in the activation of transcription factors including IRF-3, IRF-7 and a pleiotropic regulator NF-kappaB by specific phosphorylation [18].
• This strategy could be extended to nonhematopoietic tissues, as TGF-beta1 may be a pleiotropic regulator of somatic stem cell quiescence [19].

Analytical, diagnostic and therapeutic context of PLRG1

• Transcription of the PRL-1 gene increased in the rat liver remnant within a few minutes after partial hepatectomy and largely explained the increase in steady-state PRL-1 mRNA in the first few hours posthepatectomy [9].
• When treated with polyclonal anti-hPRL antibodies, all mutants were immunologically indistinguishable from the unmodified hPRL, and circular dichroism analyses indicated that their alpha-helix content was similar to that of the unmodified hormone [20].
• Each sample contained three distinct hPRL peaks on gel filtration designated as big medium, and small [21].
• An enriched fraction of human decidual cells that synthesizes and releases human PRL (hPRL) was obtained by isopycnic centrifugation of collagenase- and hyaluronidase-dispersed cells through Percoll [22].
• Up- and down-regulation of [125I]hPRL binding occurred after pretreatment of EFM-19 cell cultures with subphysiological or higher hPRL concentrations, respectively [23].

References