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αKG-driven RNA polymerase II transcription of cyclin D1 licenses malic enzyme 2 to promote cell-cycle progression
- Source :
- Cell Reports, Vol 42, Iss 7, Pp 112770- (2023)
- Publication Year :
- 2023
- Publisher :
- Elsevier, 2023.
-
Abstract
- Summary: 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.
- Subjects :
- CP: Molecular biology
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 42
- Issue :
- 7
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Reports
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.f912852c0b0b4c41b969491eb2078237
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.celrep.2023.112770