2-oxoglutarate and iron-dependent oxygenase domain-containing protein 1 (OGFOD1) expression is upregulated in a variety of cancers and has been related to poor prognosis. However, despite this significance to cancer progression, the precise oncogenic mechanism of OGFOD1 is not understood. We demonstrated that OGFOD1 plays a role in enhancing the transcriptional activity of RNA polymerase II in breast cancer cells. OGFOD1 directly binds to the C-terminal domain of RNA polymerase II to alter phosphorylation status. The elimination of OGFOD1 resulted in decreased tumor development. Additionally, cell cycle-dependent kinase 7 and cell cycle-dependent kinase 9, critical enzymes for activating RNA polymerase II, phosphorylated serine 256 of OGFOD1, whereas a non-phosphorylated mutant OGFOD1 failed to enhance transcriptional activation and tumor growth. Consequently, OGFOD1 helps promote tumor growth by enhancing RNA polymerase II, whereas simultaneous phosphorylation of OGFOD1 by CDK enzymes is essential in stimulating RNA polymerase II-mediated transcription both in vitro and in vivo, and expression of target genes.
Bibliographical noteFunding Information:
Funding: This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean government (MIST) (2012R1A3A2048767 and 2021R1A2C3006559 to H.-D.Y., NRF-2019R1A5A2027340 and 2019R1A2C2084716 to E.-J.C., and 2020R1A6A3A13071105 to H.-T.L.).
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- Cell cycle-dependent kinase
- RNA polymerase II
- Transcriptional regulation