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RelA mutants 'reconstituted' and cell cycle synchronized HCT116 Colorectal Cancer Cells

ABSTRACT: RelA mutants 'reconstituted' and cell cycle synchronized HCT116 Colorectal Cancer Cells

PROVIDER: PRJNA549297 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9313010_1.fastq.gz	Fastqsanger.gz
	SRR9313010_2.fastq.gz	Fastqsanger.gz
	SRR9313001_1.fastq.gz	Fastqsanger.gz
	SRR9313001_2.fastq.gz	Fastqsanger.gz
	SRR9313011_1.fastq.gz	Fastqsanger.gz

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RelA mutants 'reconstituted' and cell cycle synchronized HCT116 Colorectal Cancer Cells

Project description:Protein deamidation is emerging as a post-translational modification that regulates protein function. The general role of protein deamidation is emerging asn fundamental to biological processes, yet remains is poorly understood. Here, we report that the rate-limiting enzyme of pyrimidine synthesis, a trifunctional enzyme containing activity of carbamoyl phosphate synthetase, aspartyl transcarbamoylase and dihydroorotase (CAD), deamidates the RelA subunit to inactivate NF-κB and promote glycolysis. Functional screening and identified CAD as a negative regulator of NF-κB activation, and biochemical analysis demonstrated that CAD deamidatesd RelA in vitro and in cellsto negate NF-κB activation. D eamidated RelA, though failed to activate the expression of NF-κB-dependent genes, thoughbut it up-regulated that of key glycolytic enzymes to promote glycolysis and cell proliferation. In proliferating cells, CAD is activated and catalyzes de novo pyrimidine synthesis to meet the metabolic need during S phase. CAD-mediated RelA deamidation and NF-κB inactivation and glycolytic gene expression paralleled in a cell cycle-dependent mannerdriven by CAD-mediated RelA deamidation are necessary for cell proliferation. In addition, CAD promoted glycolysis via deamidated RelA that up-regulated the expression of key glycolytic enzymes. Stratification of cancer cell lines by CAD-mediated RelA deamidation predicted their sensitivity to inhibitors of glycolytic enzymes, while a subset of mutations predisposed RelA to deamidation and promoted glycolysis to enable cell proliferation. This work describes a process of metabolic reprogramming enabled by CAD-mediated RelA deamidation that underpins cell proliferation and tumorigenesis.

2019-11-01 | GSE132868 | GEO

Reconstituted Rela-/- MEF

Project description:Reconstituted Rela-/- MEF

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Reconstituted Rela-/- MEF

2019-11-01 | GSE132871 | GEO

Role of RelA:CBP/p300 interaction on RelA-activated genes

Project description:A structure-function study of NF-kB subunit RelA and coactivator CBP/p300 interaction reveals the critical role of CBP/p300 in recruitment of RelA to its target promoter site. mRNA profiles of unstimulated or stimulated with TNFa rela-/- MEF reconstituted with RelA wild type or mutants were generated by deep sequencing, in duplicate

2013-09-09 | E-GEOD-46213 | biostudies-arrayexpress

Synchronized HTC116 cells: time course

Project description:Analysis of synchronized HCT116 cells at various time points up to 10 hours following treatment with DMSO or Nocodazole.

2009-03-31 | GSE14103 | GEO

Trancriptome profiling of murine overexpression of p65/RelA mutants

Project description:Effect of overexpression of murine p65/RelA and D361 mutant and resulting fragments in DA1-3B Bcr-Abl+ murine cell lines

2022-07-27 | GSE98437 | GEO

Transcriptome profiling of murine overexpression of p65/RelA mutants II

Project description:Effect of overexpression of murine p65/RelA and D361 mutant and resulting fragments in B16 Bcr-Abl+ murine cell lines

2022-07-27 | GSE135136 | GEO

Transcriptome profiling of murine overexpression of p65/RelA mutants III

Project description:Effect of overexpression of murine p65/RelA and D361 mutant and resulting fragments in DA1-3B Bcr-Abl+ murine cell lines

2022-07-27 | GSE135137 | GEO

Transcription profiling by array of Legionella pneumophila ppGpp knockout and relA over expression mutants.

Project description:Effect of ppGpp on transcript level after RelA overexpression (90 min). The cells are constructed in our lab. They are knock-out mutants in the production of ppGpp(guanosine tetraphosphate) of Legionella, complemented with an over-expression vector containing the relA gene to express the RelA protein (responsible for the ppGpp production). The aim is to follow the gene response in Legionella pneumophila after induction of ppGpp at different time points.

2010-04-14 | E-MTAB-211 | biostudies-arrayexpress

Identification of genes responsible for RelA-dependent proliferation arrest in HMEC conditionally expressing RelA

Project description:Immuno-histochemistry for RelA in breast tumors revealed a range of staining intensity and negative correlation between RelA levels and proliferation-index in estrogen receptor-positive tumors. Conditional expression of RelA arrested proliferation in primary mammary and fallopian tube epithelial cells. RelA dependent CDK4 downregulation was responsible for activating the G1/S checkpoint and cell cycle arrest. RelA target genes, including Interferon Response Factors (IRF), were up-regulated in the arrested cells. Among the IRFs, IRF1 expression correlates with RelA expression. Suppressing IRF1 restored CDK4 levels and rescued RelA-dependent proliferation arrest analogous to abrogating the G1/S checkpoint or restoring CDK4 levels. Apart from cyclins, regulation of CDK4 by the RelA-IRF1 transcriptional network controls proliferation of breast tumors and predicts sensitivity to a CDK4/6 inhibitor.

2015-09-26 | GSE65040 | GEO

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