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The Estrogen Receptor Co-Regulator Protein, Proline Glutamic Acid and Leucine Rich Protein 1 (PELP1) Mediates Estrogen Rapid Signaling and Neuroprotection in the Brain

ABSTRACT: We examined the role of PELP1 in E2-ER-mediated transcription in the hippocampus under conditions of GCI by perfroming global transcriptome analysis. E2-treated FLOX and PELP1 FBKO mice were subjected to GCI followed by 24 h reperfusion and the isolated RNA was utilized for RNA-seq analysis. Our results demonstrated that PELP1 is needed for optimal activation of E2-regulated genes following GCI.

ORGANISM(S): Mus musculus

PROVIDER: GSE72136 | GEO | 2015/12/07

SECONDARY ACCESSION(S): PRJNA293161

REPOSITORIES: GEO

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The Estrogen Receptor Co-Regulator Protein, Proline Glutamic Acid and Leucine Rich Protein 1 (PELP1) Mediates Estrogen Rapid Signaling and Neuroprotection in the Brain

Project description:We examined the role of PELP1 in E2-ER-mediated transcription in the hippocampus under conditions of GCI by perfroming global transcriptome analysis. E2-treated FLOX and PELP1 FBKO mice were subjected to GCI followed by 24 h reperfusion and the isolated RNA was utilized for RNA-seq analysis. Our results demonstrated that PELP1 is needed for optimal activation of E2-regulated genes following GCI. Total RNA was isolated from the hippocampus of ovariectomized FLOX and PELP1 FBKO mice (implanted with E2 mini pumps) that were subjected to GCI followed by 24 h reperfusion. Illumina TruSeq RNA Sample Preparation was performed following manufacturer's protocol. Samples were run on an Illumina HiSeq 2000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat. Genes were annotated and quantified by HTSeq-DESeq pipeline.

2015-12-07 | E-GEOD-72136 | biostudies-arrayexpress

Proline Glutamic acid and Leucine rich Protein 1 (PELP1) promotes glioblastoma progression by enhancing Wnt/β-catenin signaling

Project description:We examined the transcriptional changes modulated by Proline Glutamic acid and Leucine rich Protein 1 (PELP1) by performing global transcriptome analysis. U87 cells were transfected with control siRNA or PELP1 siRNA and the RNA was isolated and utilized for RNA-seq analysis. Our results demonstrated that PELP1 modulated genes were related to inhibition of matrix metalloproteases, glioma invasion signaling, Wnt/β-catenin signaling and other pathways related to invasion and GBM signaling.

2020-04-24 | GSE131502 | GEO

Cytoplasmic Localization of Proline, Glutamic Acid, Leucine-rich Protein 1 (PELP1) Induces Breast Epithelial Cell Migration through Up-regulation of Inhibitor of κB Kinase ϵ and Inflammatory Cross-talk with Macrophages

Project description:Cytoplasmic localization of proline, glutamic acid, leucine-rich protein 1 (PELP1) is observed in ∼40% of women with invasive breast cancer. In mouse models, PELP1 overexpression in the mammary gland leads to premalignant lesions and eventually mammary tumors. In preliminary clinical studies, cytoplasmic localization of PELP1 was seen in 36% of women at high risk of developing breast cancer. Here, we investigated whether cytoplasmic PELP1 signaling promotes breast cancer initiation in models of immortalized human mammary epithelial cells (HMECs). Global gene expression analysis was performed on HMEC lines expressing vector control, PELP1-wt, or mutant PELP1 in which the nuclear localization sequence was altered, resulting in cytoplasmic localization of PELP1 (PELP1-cyto). Global gene expression analysis identified that PELP1-cyto expression in HMECs induced NF-κB signaling pathways. Western blotting analysis of PELP1-cyto HMECs showed up-regulation of inhibitor of κB kinase ϵ (IKKϵ) and increased phosphorylation of the NF-κB subunit RelB. To determine whether secreted factors produced by PELP1-cyto HMECs promote macrophage activation, THP-1 macrophages were treated with HMEC-conditioned medium (CM). PELP1-cyto CM induced changes in THP-1 gene expression as compared with control cell CM. Double conditioned medium (DCM) from the activated THP-1 cells was then applied to HMECs to determine whether paracrine signaling from PELP1-cyto-activated macrophages could in turn promote migration of HMECs. PELP1-cyto DCM induced robust HMEC migration, which was reduced in DCM from PELP1-cyto HMECs expressing IKKϵ shRNA. Our findings suggest that cytoplasmic localization of PELP1 up-regulates pro-tumorigenic IKKϵ and secreted inflammatory signals, which through paracrine macrophage activation regulates the migratory phenotype associated with breast cancer initiation.

2017-01-31 | GSE81447 | GEO

PELP1 ChIP-chip from MCF-7 cells

Project description:Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a transcriptional coactivator that has previously been shown to collaborate with nuclear receptors. Evidence from other groups suggest that PELP1 may stimulate transcription by displacing the linker histone H1 and/or by recruiting the lysine demethylase KDM1 to demethylate H3K9me2. Also known as modulator of the non-genomic activity of estrogen receptor (MNAR), PELP1 has also been implicated promoting estrogen receptor signaling from the plasma membrane. We recently identified PELP1 a factor that interacts with the macro domain of the histone variant macroH2A1. To determine if PELP1 interacts with macroH2A1 in cells, we performed PELP1 ChIP-chip from MCF-7 cells. The pattern of PELP1 bind across the genome strongly correlates with that previously determined for macroH2A1. This data combined with additional experiments allow us to conclude that macroH2A1 regulates target gene expression in part by recruiting the transcriptional coregulator PELP1. Two PELP1 ChIP-chip biological replicates from MCF-7 human breast cancer cells are included.

2014-04-24 | E-GEOD-22254 | biostudies-arrayexpress

Proline-, glutamic acid-, and leucine-rich protein 1 mediates estrogen rapid signaling and neuroprotection in the brain.

Project description:17-? estradiol (E2) has been implicated as neuroprotective in a variety of neurodegenerative disorders. However, the underlying mechanism remains unknown. Here, we provide genetic evidence, using forebrain-specific knockout (FBKO) mice, that proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), an estrogen receptor coregulator protein, is essential for the extranuclear signaling and neuroprotective actions of E2 in the hippocampal CA1 region after global cerebral ischemia (GCI). E2-mediated extranuclear signaling (including activation of extracellular signal-regulated kinase and Akt) and antiapoptotic effects [such as attenuation of JNK signaling and increase in phosphorylation of glycogen synthase kinase-3? (GSK3?)] after GCI were compromised in PELP1 FBKO mice. Mechanistic studies revealed that PELP1 interacts with GSK3?, E2 modulates interaction of PELP1 with GSK3?, and PELP1 is a novel substrate for GSK3?. RNA-seq analysis of control and PELP1 FBKO mice after ischemia demonstrated alterations in several genes related to inflammation, metabolism, and survival in PELP1 FBKO mice, as well as a significant reduction in the activation of the Wnt/?-catenin signaling pathway. In addition, PELP1 FBKO studies revealed that PELP1 is required for E2-mediated neuroprotection and for E2-mediated preservation of cognitive function after GCI. Collectively, our data provide the first direct in vivo evidence, to our knowledge, of an essential role for PELP1 in E2-mediated rapid extranuclear signaling, neuroprotection, and cognitive function in the brain.

| S-EPMC4672783 | biostudies-literature

PELP1 ChIP-chip from MCF-7 cells

2014-04-24 | GSE22254 | GEO

MCF-7 cell RNA-seq analysis of PELP1-induced gene expression

Project description:RNA-seq was performed on MCF-7 cells expressing vector control (LXSN), PELP1-wt, and PELP1-cyto

2021-07-05 | GSE126776 | GEO

Proline Glutamic acid and Leucine rich Protein 1 (PELP1) promotes glioblastoma progression by enhancing Wnt/β-catenin signaling

Project description:Proline Glutamic acid and Leucine rich Protein 1 (PELP1) promotes glioblastoma progression by enhancing Wnt/β-catenin signaling

| PRJNA543856 | ENA

Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers

Project description:We examined the transcriptional chagnes modulated by ECBI-11 by perfroming global transcriptome analysis. ZR75 cells were treated with either control or ECBI-11 in the presence of E2 for 48 h and the isolated RNA was utilized for RNA-seq analysis. Our results demonstrated that ECBI modulated several genes that are involved in cell cycle, breast cancer signaling, estrogen signaling and apoptosis.

2017-08-18 | GSE75664 | GEO

The therapeutic potential and significance of the PELP1 signaling pathway in hepatocellular carcinoma

Project description:We examined the significance and therapeutic potential of targeting PELP1 in Hepatocellular carcinoma. Total RNA were isolated from HEP3B-control Sh, and HEP3B-PELP1-Sh cells using RNeasy mini kit, and total RNA was isolated for RNA-seq analysis. Our results demonstrated that PELP1 knockdown regulates pathways related to inflammation and interferon signaling and downregulates several pathways including MYC and E2F.

2024-10-16 | GSE254860 | GEO

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