Phosphorylation of OGFOD1 by Cell Cycle-Dependent Kinase 7/9 Enhances the Transcriptional Activity of RNA Polymerase II in Breast Cancer Cells
- 주제(키워드) OGFOD1 , RNA polymerase II , transcriptional regulation , cell cycle-dependent kinase , tumorigenesis
- 주제(기타) Oncology
- 설명문(일반) [Lee, Han-Teo; Lee, Il-Hwan; Kim, Jae-Hwan; Lee, Sangho; Kwak, Sojung; Suh, Min-Young; Hwang, In-Young; Choi, Jinmi; Youn, Hong-Duk] Seoul Natl Univ, Coll Med, Ischem Hypox Dis Inst, Dept Biomed Sci,Natl Creat Res Ctr Epigenome Repr, Seoul 03080, South Korea; [Lee, Han-Teo; Lee, Sangho] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul 03080, South Korea; [Kang, Bu-Gyeong; Cha, Sun-Shin] Ewha Womans Univ, Dept Chem & Nanosci, Seoul 03760, South Korea; [Lee, Byung-Il] Natl Canc Ctr, Res Inst, Goyang Si 10408, South Korea; [Lee, Sang-Eun] Univ Ulsan, Cardiol Asan Med Ctr, Coll Med, Seoul 05505, South Korea; [Choi, Jinmi; Cho, Eun-Jung] Sungkyunkwan Univ, Coll Pharm, Suwon 16419, South Korea; [Roe, Jae-Seok] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biochem, Seoul 03722, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 MDPI
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000182320
- 본문언어 영어
- Published As http://dx.doi.org/10.3390/cancers13143418
초록/요약
Simple Summary Among the causes of accelerating cancer properties, dysregulated transcription is considerably prominent in many cancers. However, it is difficult to target transcriptional machineries due to their fundamental importance. Compared to breast cancer cell lines, we found that OGFOD1 aggravates cancers by enhancing RNA polymerase II transcriptional activity and it is improved by cell cycle-dependent kinases. Overall, we uncovered the novel mechanism for how OGFOD1 maliciously functions in breast cancers, suggesting it as a rational cancer treatment target protein. 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.
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