Tag: FOXO

Ketogenesis-generated β-hydroxybutyrate is an epigenetic regulator of CD8 + T-cell memory development | Nature Cell Biology

Ketogenesis-generated β-hydroxybutyrate is an epigenetic regulator of CD8 + T-cell memory development | Nature Cell Biology

“Glycogen has long been considered to have a function in energy metabolism. However, our recent study indicated that glycogen metabolism, directed by cytosolic phosphoenolpyruvate carboxykinase Pck1, controls the formation and maintenance of CD8+ memory T (Tmem) cells by regulating redox homeostasis1. This unusual metabolic program raises the question of how Pck1 is upregulated in CD8+ Tmem cells. Here, we show that mitochondrial acetyl coenzyme A is diverted to the ketogenesis pathway, which indirectly regulates Pck1 expression. Mechanistically, ketogenesis-derived β-hydroxybutyrate is present in CD8+ Tmem cells; β-hydroxybutyrate epigenetically modifies Lys 9 of histone H3 (H3K9) of Foxo1 and Ppargc1a (which encodes PGC-1α) with β-hydroxybutyrylation, upregulating the expression of these genes.”

https://www.nature.com/articles/s41556-019-0440-0?utm_source=researcher_app&utm_medium=referral&utm_campaign=RESR_MRKT_Researcher_inbound

KLF2 induces the senescence of pancreatic cancer cells by cooperating with FOXO4 to upregulate p21 – ScienceDirect

KLF2 induces the senescence of pancreatic cancer cells by cooperating with FOXO4 to upregulate p21 – ScienceDirect

“In this study, we showed that overexpression of KLF2 induced the senescence of pancreatic cancer cells and inhibited tumorigenesis, and knockdown of KLF2 inhibited senescence and p21 expression. In the molecular mechanism study, KLF2 was found to interact with FOXO4 and cooperated with FOXO4 to induce the expression of p21.”

https://www.sciencedirect.com/science/article/pii/S001448271930669X