Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SERBP1 deacetylation inhibits ferroptosis to promote KSHV-induced cellular transformation by decaying lipoyltransferase 2 mRNA

ABSTRACT: Ferroptosis, a defensive strategy employed by the host to restrict pathogenic infections, has been implicated in the development and therapeutic responses of various types of tumors. However, the role of ferroptosis in KSHV-induced malignant tumors remains elusive. A steadily growing number of non-histone proteins have been identified as acetylation targets, their functions have yet to be revealed. In this study, we obtained a marked disparity in the landscape of acetylation between MM and KSHV-transformed MM (KMM) cells. SERBP1 deacetylation was upregulated in KMM cells and contributed to KSHV-induced cellular transformation by inhibiting ferroptosis. Mechanistically, KSHV-encoded viral interleukin-6 (vIL-6) hijacks SIRT3, a mitochondrial NAD+-dependent deacetylase, to interact with SERBP1 leading to the deacetylation of SERBP1. Deacetylated SERBP1 exhibits reduced binding to Lipt2 mRNA, which promotes Lipt2 mRNA degradation, resulting in ferroptosis inhibition. Our findings unveil a novel role of SERBP1 deacetylation in regulating ferroptosis and KSHV-induced cellular transformation and identify potential new therapeutic targets for KSHV infection and KSHV-induced cancers.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE241111 | GEO | 2023/08/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data in KSHV-infected primary rat mesenchymal precursor (MM) cells

2013-08-28 | GSE50381 | GEO

Prolonged Kaposi's Sarcoma-associated Herpesvirus vIL-6 Exposure Enhances Inflammatory Responses by Epigenetic Reprogramming (CUT&RUN)

Project description:Kaposi sarcoma-associated herpesvirus (KSHV) inflammatory cytokine syndrome (KICS) is a newly described chronic inflammatory disease condition caused by KSHV infection and is characterized by high KSHV viral load and sustained elevations of serum KSHV-encoded IL-6 (vIL-6) and human IL-6 (hIL-6). KICS has significant immortality and possesses greater risks of having other complications, which include malignancies. Although prolonged inflammatory vIL-6 exposure by persistent KSHV infection is expected to have key roles in subsequent disease development, the biological effects of prolonged vIL-6 exposure remain elusive. Using thiol(SH)-Linked Alkylation for the Metabolic Sequencing (SLAM-seq) and Cleavage Under Target & Release Using Nuclease (CUT&RUN) analysis, we studied the effect of prolonged vIL-6 exposure in chromatin landscape and resulting cytokine production. The studies showed that prolonged vIL-6 exposure increased Bromodomain containing 4 (BRD4) and histone H3 lysine 27 acetylation (H3K27Ac) co-occupancies on chromatin, and the recruitment sites were frequently co-localized with poised RNA polymerase II with associated enzymes. Increased BRD4 recruitment on promoters was associated with increased and prolonged p65 (RelA) binding after the LPS stimulation. The p65 binding resulted in quicker and sustained transcription bursts from the promoters; this mechanism increased total amounts of hIL-6 and IL-10 in tissue culture. Pretreatment with the BRD4 inhibitor, OTX015, eliminated the enhanced inflammatory cytokine production. These findings suggest that persistent vIL-6 exposure may establish a chromatin landscape favorable for the reactivation of inflammatory responses in monocytes. This epigenetic memory may explain the greater risk of chronic inflammatory disease development in KSHV-infected individuals.

2023-08-08 | GSE233323 | GEO

Prolonged Kaposi's Sarcoma-associated Herpesvirus vIL-6 Exposure Enhances Inflammatory Responses by Epigenetic Reprogramming (SLAM-seq)

2023-08-08 | GSE233119 | GEO

Prolonged Kaposi's Sarcoma-associated Herpesvirus vIL-6 Exposure Enhances Inflammatory Responses by Epigenetic Reprogramming (RNA-seq)

2023-08-08 | GSE232843 | GEO

Expression data in KSHV-infected primary rat mesenchymal precursor (MM) cells

Project description:Kaposi's sarcoma-associated herpesvirus (KSHV) can efficiently infect and transform primary rat mesenchymal precursor (MM) cells. Regulation of cell cycle progression and apoptosis by KSHV-encoded microRNAs is required for KSHV-induced cellular transformation and tumorigenesis. To determine the roles of KSHV miRs in growth deregulation, we infected MM cells with the KSHV miR cluster deletion mutant and monitored infection by examining green fluorescence protein expression from a cassette inserted in the KSHV genome.

2013-08-28 | E-GEOD-50381 | biostudies-arrayexpress

Hijacking of Nucleotide Biosynthesis and Deamidation-mediated Glycolysis by an Oncogenic Herpesvirus

Project description:Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma (KS) and multiple types of B cellmalignancies. Emerging evidence demonstrates that KSHV reprograms host-cell central carbon metabolic pathways, which contributesto viral persistence and tumorigenesis. However, the mechanisms underlying KSHV-mediated metabolic reprogramming remain poorlyunderstood. Carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) is a key enzyme of the denovo pyrimidine synthesis, and was recently identified to deamidate the NF-κB subunit RelA to promote aerobic glycolysis and cellproliferation. Here we report that KSHV infection exploits CAD for nucleotide synthesis and glycolysis. Mechanistically, KSHV vCyclin binds to and hijacks cyclin-dependent kinase CDK6 to phosphorylate Ser-1900 on CAD, thereby activating CAD-mediatedpyrimidine synthesis and RelA-deamidation-mediated glycolytic reprogramming. Correspondingly, genetic depletion orpharmacological inhibition of CDK6 and CAD potently impeded KSHV lytic replication and thwarted tumorigenesis of primaryeffusion lymphoma (PEL) cells in vitro and in vivo. Altogether, our work defines a viral metabolic reprogramming mechanismunderpinning KSHV oncogenesis, which may spur the development of new strategies to treat KSHV-associated malignancies and otherdiseases.

2024-02-16 | PXD043435 | Pride

EP300 promotes ferroptosis via HSPA5 acetylation in pancreatic cancer

Project description:Ferroptosis is a form of regulated cell death characterized by oxidative injury-induced lipid peroxidation. However, the detailed protein post-translational modification regulatory mechanism of ferroptosis remains largely unknown. Here, we report that E1A binding protein P300 (EP300) acetyltransferase promotes ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells via the acetylation of heat shock protein family A (Hsp70) member 5 (HSPA5, also known as GRP78 or BIP) on the site of K353. Acetylated HSPA5 loses its ability to inhibit lipid peroxidation and subsequent ferroptotic cell death. Genetic or pharmacological inhibition of EP300-mediated HSPA5 acetylation on K353 increases PDAC cell resistance to ferroptosis. Moreover, histone deacetylase 6 (HDAC6) limits HSPA5 acetylation and subsequent ferroptosis.

2023-10-24 | PXD039998 | Pride

KSHV uses viral IL6 to expand infected immunosuppressive macrophages (scRNA-seq)

Project description:Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic double-stranded DNA virus and the etiologic agent of Kaposi’s sarcoma and hyperinflammatory lymphoproliferative disorders. Understanding the mechanism by which KSHV increases infected cell populations is crucial for curing KSHV-associated diseases. Here, we demonstrate that KSHV preferentially infects CD14+ monocytes and sustains viral replication through the viral interleukin-6 (vIL-6)-mediated activation of STAT1 and 3. Using vIL6-sufficient and vIL6-deficient recombinant KSHV, we demonstrated that vIL6 plays a critical role in promoting the proliferation and differentiation of KSHV-infected monocytes into macrophages. The macrophages derived from vIL6-sufficient (wild type) KSHV infection showed a distinct transcriptional profile of elevated IFN-pathway activation with immune suppression and were compromised in T-cell stimulation function compared to those from vIL6-deficient KSHV infection or uninfected control. These results highlight a clever strategy, in which KSHV utilizes vIL6 to secure its initial viral pool by expanding infected dysfunctional macrophages. This mechanism also facilitates KSHV to escape from host immune surveillance and to establish a lifelong infection.

2023-08-30 | GSE227166 | GEO

KSHV uses viral IL6 to expand infected immunosuppressive macrophages (RNA-seq)

2023-08-30 | GSE227163 | GEO

Proteomic shift in mouse embryonic fibroblasts Pfa1 during erastin-induced ferroptosis

Project description:This report provides data on ferroptosis induced proteomic response in immortalized mouse embryonic fibroblasts which are 4-OH-TAM-inducible Gpx4−/− (referred to as Pfa1 cells). Pfa1 cells are a valuable, widespread and well characterized model for ferroptosis research. In the first part of this batch, we used Erastin to induce ferroptosis and collected samples at 0h, 24h and 48h after treatment. Untreated cells were used as a control. In the second part, we tested Liproxtatin-1 ferroptosis inhibitor on Tamoxifen-induced Pfa1 cells after 0h, 24h, 48h. Tamoxifen-induced ferroptosis activation of these cells are in PRIDE PXD040094. Pfa1 cells (a kind gift from Marcus Conrad, Munich) were cultured in RPMI-1640 media (2 g/L glucose, 10% FBS, 2 mM Gibco GlutaMAX Supplement, 1% pen/strep) at 37C with 5% CO2 in a humidified incubator. Cells (300k) were seeded on Corning 100 mm tissue-culture treated culture dishes and incubated overnight. On the next day Pfa1 cells were treated with or without 0.5 µM erastin (E7781, Sigma-Aldrich). For experiment on ferroptosis inhibition Pfa1 cells were treated with or without 1 µM Tamoxifen and 0.5 µM Liproxtatin-1 simultaneously.

2023-07-11 | PXD041463 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data