PIM1 phosphorylation of the androgen receptor and 14-3-3 ζ coordinates their interaction and chromatin occupancy to regulate gene transcription in prostate cancer
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PROVIDER: PRJNA751077 | ENA |
REPOSITORIES: ENA
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Project description:We previously identified 14-3-3 ζ S64 as a substrate of PIM1 in an in vivo chemical genetic screen. To verify this phosphorylation event and determine whether S64 is the predominant phosphorylation site, we performed in vitro phosphorylation of 14-3-3 ζ by PIM1.
2021-11-25 | PXD023623 | Pride
Project description:We used ChIP-seq to identify chromatin binding sites for AR, 14-3-3 ζ, and pS213 AR in the absence and presence of PIM1 over-expression. We find that, as expected, pS213 AR occupancy almost completely overlaps with total AR occupancy, and increases in the presence of PIM1 over-expression. Additionally, the majority of pS213 AR sites are co-occupied by 14-3-3 ζ. 14-3-3 ζ is a known AR co-activator, but this study definitively shows its co-occupancy on chromatin with AR and pS213 AR.
2021-11-03 | GSE181224 | GEO
Project description:14-3-3 ζ is an androgen receptor (AR) co-activator. To further understand how 14-3-3 ζ may be modulating AR activity, we performed rapid immunoprecipitation mass spectrometry of endogenous proteins for analysis of chromatin complexes (RIME) on AR and 14-3-3 ζ in LNCaP prostate cancer cells in the presence of PIM1. This enabled us to observe what other proteins associate with both 14-3-3 ζ and AR on chromatin. Notably, several of the proteins we identified as associated with both AR and 14-3-3 ζ are known AR co-regulators. We hypothesized that to co-regulate AR, 14-3-3 ζ may be recruiting or altering interactions between AR and AR co-regulators.
2021-11-25 | PXD023634 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-11-03 | GSE181226 | GEO
Project description:The Pim (proviral integration site for Moloney murine leukemia virus) proteins form a serine threonine kinase family that regulates cell proliferation, migration and cell survival. Here we demonstrate for the first time that a Pim1 kinase plays an essential role in antiviral innate immune responses. Specifically, our in vivo, in vitro and RNA-sequencing analyses showed that Pim1 was quickly upregulated after Toll-like receptor (TLR) stimulation in a NF-kB-dependent manner and then promoted IFN-b production by forming a cell-surface complex composed of TRIF-signaling molecules and IRF3 that promoted IRF3 phosphorylation, nuclear translocation, and IFN-b production. As shown by Pim1 knockdown and knockout, Pim1 was essential for this role but its kinase activity was not involved. Pim1-deficiency increased the susceptibility of mice to poly I:C-induced sepsis. Our study uncovers a previously unrecognized role for Pim1 in antiviral innate immune responses, thus providing a new target for controlling viral infection.
2022-12-14 | GSE195582 | GEO
Project description:Genome-wide maps of the androgen receptor, pS213 androgen receptor, and 14-3-3 ζ chromatin occupancy in control and PIM1 over-expressing LNCaP cells
| PRJNA751082 | ENA
Project description:Background: PIM1 is a constitutively active serine-threonine kinase regulating cell survival and proliferation. Increased PIM1 expression has been correlated with cancer metastasis by facilitating migration and anti-adhesion. Endothelial cells play a pivotal role in these processes by contributing a barrier to the blood stream. Here, we investigated whether PIM1 regulates mouse aortic endothelial cell (MAEC) monolayer integrity. Methods: Pim1-/-MAEC were isolated from Pim1 knockout mice and used in trypsinization-, wound closure assays, electrical cell-substrate sensing, immunostaining, cDNA transfection and as RNA source for microarray analysis. Results: Pim1-/-MAEC displayed decreased migration, slowed cell detachment and increased electrical resistance across the endothelial monolayer. Reintroduction of Pim1- cDNA into Pim1-/-MAEC significantly restored wildtype adhesive characteristics. Pim1-/--MAEC displayed enhanced focal adhesion and adherens junction structures containing vinculin and M-NM-2-catenin, respectively. Junctional molecules such as Cadherin 13 and matrix components such as Collagen 6a3 were highly upregulated in Pim1-/- cells. Intriguingly, extracellular matrix deposited by Pim1-/- cells alone was sufficient to induce the hyperadhesive phenotype in wildtype endothelial cells. Conclusion: Loss of Pim1 induces a strong adhesive phenotype by enhancing endothelial cell-cell and cell-matrix adhesion by the deposition of a specific extracellular matrix. Targeting PIM1 function therefore might be important to promote endothelial barrier integrity. Pim-1-/- mouse aortic endothelial cells were compared to wildtype cells
2012-10-29 | E-GEOD-32059 | biostudies-arrayexpress
Project description:It has been estimated that about 11% of cellular genes present a functional E box to which MYC can associate on the genome. MYC silencing demonstrated that MYC recruits PIM1 at specific MYC binding sites and confocal microscopy following growth factor treatment, showed an elevated degree of nuclear co-localization of PIM1 with nascent transcripts and with MYC suggesting that PIM1 is recruited by MYC to a large number of sites. To understand the actual extension of PIM1 and MYC co-operation in gene transcription we performed expression profile analysis of 293 cells silenced either for MYC or PIM1 at 120 minutes after serum treatment. MYC silencing affected the expression of 1026 genes of which 818 were up-regulated and 208 were down-regulated. Comparison of genes regulated by MYC with those regulated by PIM1, by RNAi silencing, showed that PIM1 contributes to the regulation of 207 genes out of the 1026 MYC-regulated genes. Thus, a subset of 20% of MYC-regulated genes, are also regulated by PIM1. The co-regulated includes genes involved in cell metabolism, protein synthesis, cycle progression, and oncogenesis. Interestingly, a large number of genes are transcriptional factors, which suggests that PIM1 participates in MYC-dependent regulatory networks. Keywords: expression profiles
2007-07-31 | GSE7960 | GEO
Project description:It has been estimated that about 11% of cellular genes present a functional E box to which MYC can associate on the genome. MYC silencing demonstrated that MYC recruits PIM1 at specific MYC binding sites and confocal microscopy following growth factor treatment, showed an elevated degree of nuclear co-localization of PIM1 with nascent transcripts and with MYC suggesting that PIM1 is recruited by MYC to a large number of sites. To understand the actual extension of PIM1 and MYC co-operation in gene transcription we performed expression profile analysis of 293 cells silenced either for MYC or PIM1 at 120 minutes after serum treatment. MYC silencing affected the expression of 1026 genes of which 818 were up-regulated and 208 were down-regulated. Comparison of genes regulated by MYC with those regulated by PIM1, by RNAi silencing, showed that PIM1 contributes to the regulation of 207 genes out of the 1026 MYC-regulated genes. Thus, a subset of 20% of MYC-regulated genes, are also regulated by PIM1. The co-regulated includes genes involved in cell metabolism, protein synthesis, cycle progression, and oncogenesis. Interestingly, a large number of genes are transcriptional factors, which suggests that PIM1 participates in MYC-dependent regulatory networks. Experiment Overall Design: The gene expression analysis was performed by hybridizing RNA samples to the Whole Human Genome Oligo Microarray from Agilent Technologies. Samples were obtained from 293 cells, treated with serum for 120 minutes, expressing either two independent MYC shRNA (shMYC#1 and shMYC#2) or their relative scrambled shRNA (shsM#1 and shsM#2) for MYC expression analysis; two independent PIM1 shRNA (shPIM1#1 and shPIM1#2) or their relative scrambled shRNA (shsP#1 and shsP#2) for PIM1 expression analysis.
2008-06-15 | E-GEOD-7960 | biostudies-arrayexpress
Project description:Background: PIM1 is a constitutively active serine-threonine kinase regulating cell survival and proliferation. Increased PIM1 expression has been correlated with cancer metastasis by facilitating migration and anti-adhesion. Endothelial cells play a pivotal role in these processes by contributing a barrier to the blood stream. Here, we investigated whether PIM1 regulates mouse aortic endothelial cell (MAEC) monolayer integrity. Methods: Pim1-/-MAEC were isolated from Pim1 knockout mice and used in trypsinization-, wound closure assays, electrical cell-substrate sensing, immunostaining, cDNA transfection and as RNA source for microarray analysis. Results: Pim1-/-MAEC displayed decreased migration, slowed cell detachment and increased electrical resistance across the endothelial monolayer. Reintroduction of Pim1- cDNA into Pim1-/-MAEC significantly restored wildtype adhesive characteristics. Pim1-/--MAEC displayed enhanced focal adhesion and adherens junction structures containing vinculin and β-catenin, respectively. Junctional molecules such as Cadherin 13 and matrix components such as Collagen 6a3 were highly upregulated in Pim1-/- cells. Intriguingly, extracellular matrix deposited by Pim1-/- cells alone was sufficient to induce the hyperadhesive phenotype in wildtype endothelial cells. Conclusion: Loss of Pim1 induces a strong adhesive phenotype by enhancing endothelial cell-cell and cell-matrix adhesion by the deposition of a specific extracellular matrix. Targeting PIM1 function therefore might be important to promote endothelial barrier integrity.
2012-10-29 | GSE32059 | GEO