Reconstituted Rela-/- MEF
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA549298 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9313015.fastq.gz | Fastqsanger.gz | |||
| SRR9313016.fastq.gz | Fastqsanger.gz | |||
| SRR9313017.fastq.gz | Fastqsanger.gz | |||
| SRR9313018.fastq.gz | Fastqsanger.gz |
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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.
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