细胞周期
细胞周期蛋白D1
RNA聚合酶Ⅱ
细胞生物学
生物
细胞周期蛋白
抄写(语言学)
细胞周期蛋白
异柠檬酸脱氢酶
基因表达
分子生物学
细胞
发起人
基因
酶
生物化学
语言学
哲学
作者
Yefeng Yang,Zhenxi Zhang,Wei Li,Yan Si,Li Li,Wenjing Du
出处
期刊:Cell Reports
[Elsevier]
日期:2023-07-01
卷期号:42 (7): 112770-112770
被引量:1
标识
DOI:10.1016/j.celrep.2023.112770
摘要
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.
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