A UL26-PIAS1 complex antagonizes anti-viral gene expression during Human Cytomegalovirus infection
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ABSTRACT:
PROVIDER: PRJNA1103198 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28773369.fastq.gz | Fastqsanger.gz | |||
| SRR28773370.fastq.gz | Fastqsanger.gz | |||
| SRR28773371.fastq.gz | Fastqsanger.gz | |||
| SRR28773372.fastq.gz | Fastqsanger.gz | |||
| SRR28773373.fastq.gz | Fastqsanger.gz |
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Project description:Viral disruption of innate immune signaling is a critical determinant of productive infection. The Human Cytomegalovirus (HCMV) UL26 protein prevents anti-viral gene expression during infection, yet the mechanisms involved are unclear. We used TurboID-driven proximity proteomics to identify putative UL26 interacting proteins during infection to address this issue. We find that UL26 forms a complex with several immuno-regulatory proteins, including several STAT family members and various PIAS proteins, a family of E3 SUMO ligases. Our results indicate that UL26 prevents STAT phosphorylation during infection and antagonizes transcriptional activation induced by either interferon α (IFNA) or tumor necrosis factor α (TNFα). Additionally, we find that the inactivation of PIAS1 sensitizes cells to inflammatory stimulation, resulting in an anti-viral transcriptional environment similar to ΔUL26 infection. Further, PIAS1 is important for HCMV cell-to-cell spread, which depends on the presence of UL26, suggesting that the UL26-PIAS1 interaction is vital for modulating intrinsic anti-viral defense.
2024-04-27 | GSE264589 | GEO
Project description:To study the effect of PIAS1 on transcriptional regulation, we establishedstable PIAS1 shRNA knockdown cells in breast cancer cell line MDA-MB231. By comparing the expression profiles of control vs PIAS1 knockdown cells, we can identify potential PIAS1 target genes involved in breast tumorigenesis.
2014-02-06 | GSE44024 | GEO
Project description:To study the effect of PIAS1 on transcriptional regulation, we establishedstable PIAS1 shRNA knockdown cells in breast cancer cell line MDA-MB231. By comparing the expression profiles of control vs PIAS1 knockdown cells, we can identify potential PIAS1 target genes involved in breast tumorigenesis. MDA-MB231 Control shRNA and PIAS1 shRNA2 cells were cultured in DMEM plus 10% FBS (DMEM) or SCM for 30 h, and total RNA was used for microarray.
2014-02-06 | E-GEOD-44024 | biostudies-arrayexpress
Project description:To study the importance of PIAS1 (protein inhibitor of activated STAT1) for the androgen-regulated transcriptome of VCaP prostate cancer cells, we silenced its expression by RNAi. Transcriptome analyses revealed that a subset of the androgen-regulated genes is significantly influenced, either activated or repressed, by PIAS1 depletion. The depletion also exposed a completely new set of genes to androgen regulation, suggesting that PIAS1 can mask genes from androgen receptor (AR). Pathway analyses of gene expression data suggest involvement of PIAS1 in VCaP cell proliferation. According to genome-wide ChIP-seq analyses, PIAS1 interacts with the AR on chromatin harboring also SUMO2/3, as androgen exposure multiplied the occupancy of PIAS1 in the chromatin, and resulted in nearly complete overlap with AR chromatin binding events. PIAS1 interacted also with pioneer factor FOXA1 in the chromatin. Our results strongly suggest that PIAS1 is a genuine chromatin-bound coregulator of AR which functions in a target gene selective fashion in prostate cancer cells.
2015-01-02 | GSE56086 | GEO
Project description:The Protein Inhibitor of Activated STAT 1 (PIAS1) is an E3 SUMO ligase that plays important roles in various cellular pathways, including STAT signaling, p53 pathway, and the steroid hormone signaling pathway. PIAS1 can SUMOylate PML (at Lys-65 and Lys-160) and PML-RARα promoting their ubiquitin-mediated degradation. Increasing evidence shows that PIAS1 is overexpressed in various human malignancies, such as prostate and lung cancers. To understand the mechanism of action of PIAS1, we developed a quantitative SUMO proteomic approach to identify potential substrates of PIAS1 in a system-wide manner. Our analyses enabled the profiling of 983 SUMO sites on 544 proteins, of which 204 SUMO sites on 123 proteins were identified as putative PIAS1 substrates. These substrates were found to be involved in different cellular processes, including transcriptional regulation, DNA binding and cytoskeleton dynamics. Further functional studies on Vimentin (VIM), a type III intermediate filament protein involved in cytoskeleton organization and cell motility, revealed that PIAS1 exerts its effects on cell migration and cell invasion through the SUMOylation of VIM at Lys-439 and Lys-445 residues. VIM SUMOylation was necessary for its dynamic disassembly, and cells expressing a non-SUMOylatable VIM mutant showed reduced levels of proliferation and migration. Our approach not only provides a novel strategy for the identification of E3 SUMO ligase substrates, but also yields valuable biological insights into the unsuspected role of PIAS1 and VIM SUMOylation on cell motility.
2020-02-06 | PXD011932 | Pride
Project description:Epstein-Barr virus nuclear antigen 1 (EBNA1) is essential for the replication and stable maintenance of the viral episome in infected cells. Here, we identify the SUMO E3 ligase PIAS1 as a key regulator of EBNA1 through site-specific SUMOylation. Our Chromatin-Immunoprecipitation Sequencing (ChIP-seq) analysis revealed that PIAS1 is enriched at the viral origin of plasmid replication (oriP), where it physically associates with EBNA1 and catalyzes its SUMOylation. Using mutational analysis, we identified three lysine residues on EBNA1 (K17, K75, and K241) as major SUMOylation sites. Disruption of these sites compromises EBNA1’s ability to restrict EBV lytic replication. In addition, both PIAS1 depletion and the disruption of EBNA1 SUMOylation lead to reduced retention of EBNA1-OriP-based EBV mini-replicon, indicating the importance of EBNA1 SUMOylation in viral episome maintenance. Together, these results uncover a conserved post-translational mechanism by which PIAS1-mediated SUMOylation modulates EBNA1 function and EBV episome maintenance and suggests a broader role for SUMOylation in viral latency, lytic replication and persistence.
2025-12-01 | GSE306456 | GEO
Project description:Microarray analysis was designed to study the effect of PIAS1 on interferon (IFN) signaling pathway by comparing the gene activation profiles of wild type and Pias1 null cells in response to IFN treatments. Microarray analysis was performed essentially following the manufacturer's instructions (Affymetrix). Briefly, bone marrow-derived macrophages (BMMs) from wile type or Pias1 null littermates were either untreated, or treated with IFN-beta (500 U/ml) or IFN-gamma (10 ng/ml) for 2h or 4h. Total RNA was prepared with RNA-STAT60 (TEL-TEST) and purified with the RNeasy kit (Qiagen). Double stranded complementary DNA was synthesized from 20 ug of total RNA according to Affymetrix methodology, and purified with Phase Lock Gels (Eppendorf). Biotin-labeled RNA was synthesized with the BioArray High Yield RNA Transcript Labeling Kit (Enzo). Samples were cleaned, fragmentated and hybridized to murine genome (MGU74Av2) Genechips (Affymetrix) as instructed. GeneChips were stained with phycoerythrin-streptavidin (Molecular Probes) and scanned with a GeneChip scanner (Affymetrix).
2007-10-10 | E-GEOD-1552 | biostudies-arrayexpress
Project description:Analysis of PIAS1 co-regulation in the androgen signaling pathways in prostate cancer cell line. VCaP cells were exposed to control (siSCR) or PIAS1 (siPIAS1) targeted siRNA for 96h. After 16h of 100 nM testosterone (or without) treatment the total RNA was isolated, each treatment included three replicates.
2013-01-01 | E-GEOD-30316 | biostudies-arrayexpress
Project description:Microarray analysis was designed to study the effect of PIAS1 on interferon (IFN) signaling pathway by comparing the gene activation profiles of wild type and Pias1 null cells in response to IFN treatments. Microarray analysis was performed essentially following the manufacturer’s instructions (Affymetrix). Briefly, bone marrow-derived macrophages (BMMs) from wile type or Pias1 null littermates were either untreated, or treated with IFN-beta (500 U/ml) or IFN-gamma (10 ng/ml) for 2h or 4h. Total RNA was prepared with RNA-STAT60 (TEL-TEST) and purified with the RNeasy kit (Qiagen). Double stranded complementary DNA was synthesized from 20 ug of total RNA according to Affymetrix methodology, and purified with Phase Lock Gels (Eppendorf). Biotin-labeled RNA was synthesized with the BioArray High Yield RNA Transcript Labeling Kit (Enzo). Samples were cleaned, fragmentated and hybridized to murine genome (MGU74Av2) Genechips (Affymetrix) as instructed. GeneChips were stained with phycoerythrin-streptavidin (Molecular Probes) and scanned with a GeneChip scanner (Affymetrix). Keywords: parallel sample
2004-07-16 | GSE1552 | GEO
Project description:The majority of breast cancer subtypes express androgen receptor (AR) in addition to estrogen receptor α (ERα). Depending on the breast cancer subtype androgen signaling has either stimulatory or inhibitory roles in breast cancer cell growth. We have mapped AR cistrome in ERα negative human molecular apocrine breast cancer MDA-MB453 cells and analyzed it in relation to the androgen-regulated transcriptome in the same cells. We have also examined the effect of silencing of the coregulator SUMO ligase PIAS1 on the androgen-regulated transcriptome and AR cistrome in MDA-MB453 cells. Our results show that the MDA-MB453 cells share with VCaP prostate cancer cells a core AR cistrome and target gene signature linked to cancer cell growth and that PIAS1 acts as an AR target gene-selective coregulator in MDA-MB453 cells. MDA-MB453 cells were transfected with control siRNA (siNON) or PIAS1 siRNA (siPIAS1) for 72 h and treated 16 h with 10 nM R1881 or vehicle (ethanol). Total RNA was isolated and biological triplicate samples were analyzed by microarray.
2016-07-18 | E-GEOD-70162 | biostudies-arrayexpress