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Cell Rep ; 42(7): 112770, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37422761

RESUMO

Increased metabolic activity usually provides energy and nutrients for biomass synthesis and is indispensable for the progression of the cell cycle. Here, we find a role for α-ketoglutarate (αKG) generation in regulating cell-cycle gene transcription. A reduction in cellular αKG levels triggered by malic enzyme 2 (ME2) or isocitrate dehydrogenase 1 (IDH1) depletion leads to a pronounced arrest in G1 phase, while αKG supplementation promotes cell-cycle progression. Mechanistically, αKG directly binds to RNA polymerase II (RNAPII) and increases the level of RNAPII binding to the cyclin D1 gene promoter via promoting pre-initiation complex (PIC) assembly, consequently enhancing cyclin D1 transcription. Notably, αKG addition is sufficient to restore cyclin D1 expression in ME2- or IDH1-depleted cells, facilitating cell-cycle progression and proliferation in these cells. Therefore, our findings indicate a function of αKG in gene transcriptional regulation and cell-cycle control.


Assuntos
Ciclina D1 , Ácidos Cetoglutáricos , Ciclina D1/genética , Ciclina D1/metabolismo , Ácidos Cetoglutáricos/metabolismo , RNA Polimerase II , Ciclo Celular , Fase G1
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