Phosphorylation of ogfod1 by cell cycle-dependent kinase 7/9 enhances the transcriptional activity of rna polymerase ii in breast cancer cells

Han Teo Lee, Il Hwan Lee, Jae Hwan Kim, Sangho Lee, Sojung Kwak, Min Young Suh, In Young Hwang, Bu Gyeong Kang, Sun Shin Cha, Byung Il Lee, Sang Eun Lee, Jinmi Choi, Jae Seok Roe, Eun Jung Cho, Hong Duk Youn

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Article number3418
JournalCancers
Volume13
Issue number14
DOIs
StatePublished - 2 Jul 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Cell cycle-dependent kinase
  • OGFOD1
  • RNA polymerase II
  • Transcriptional regulation
  • Tumorigenesis

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