Transcriptional regulation of amino acid metabolism by KDM2B, in the context of ncPRC1.1 and in concert with MYC and ATF4.
Evangelia ChavdoulaVollter AnastasAlessandro La FerlitaJulian AldanaGiuseppe CarotaMariarita SpampinatoBurak SoysalIlaria CosentiniSameer ParasharAnuvrat SircarGiovanni NigitaLalit SehgalMichael A FreitasPhilip N TsichlisPublished in: bioRxiv : the preprint server for biology (2023)
The knockdown of KDM2B in basal-like breast cancer cell lines lowers the levels of GSH and sensitizes the cells to ROS inducers, GSH targeting molecules, and DUB inhibitors.KDM2B regulates intermediary metabolism by targeting the expression of a host of metabolic enzymes, including those in the SGOC, glutamate, and GSH metabolism.KDM2B enhances chromatin accessibility of MYC and ATF4 and promotes their expression.MYC and ATF4 binding sites are enriched in the promoters of genes whose accessibility depends on KDM2B.KDM2B functioning in the context of ncPRC1.1, binds the promoters of transcriptionally active genes, including those encoding KDM2B-regulated metabolic enzymes, in concert with MYC and ATF4.Basal-like TNBCs expressing high levels of all three regulators, exhibit a distinct metabolic signature that is associated with poor prognosis.
Keyphrases
- transcription factor
- poor prognosis
- long non coding rna
- genome wide identification
- endoplasmic reticulum stress
- induced apoptosis
- genome wide
- amino acid
- dna damage
- fluorescent probe
- cell death
- gene expression
- signaling pathway
- cell proliferation
- young adults
- binding protein
- reactive oxygen species
- bioinformatics analysis
- cell cycle arrest