Kim Jae-Hwan, Lee Soon-Min, Lee Jong-Hyuk, Chun Sohyun, Kang Byung-Hee, Kwak Sojung, Roe Jae-Seok, Kim Tae Wan, Kim Hyunsoo, Kim Woo Ho, Cho Eun-Jung, Youn Hong-Duk
National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, Republic of Korea.
Oncotarget. 2015 Aug 14;6(23):19528-41. doi: 10.18632/oncotarget.3683.
2-oxogluatrate and Fe(II)-dependent oxygenase domain-containing protein 1 (OGFOD1) was recently revealed to be a proline hydroxylase of RPS23 for translational termination. However, OGFOD1 is nuclear, whereas translational termination occurs in the cytoplasm, raising the possibility of another function of OGFOD1 in the nucleus. In this study, we demonstrate that OGFOD1 is involved in cell cycle regulation. OGFOD1 knockdown in MDA-MB-231 breast cancer cells significantly impeded cell proliferation and resulted in the accumulation of G1 and G2/M cells by decreasing the mRNA levels of G1/S transition- and G2/M-related transcription factors and their target genes. We also confirmed that OGFOD1 is highly expressed in breast cancer tissues by bioinformatic analysis and immunohistochemistry. Thus, we propose that OGFOD1 is required for breast cancer cell proliferation and is associated with poor prognosis in breast cancer.
最近发现，2-氧代戊二酸和含铁（II）的含加氧酶结构域蛋白1（OGFOD1）是核糖体蛋白S23（RPS23）用于翻译终止的脯氨酸羟化酶。然而，OGFOD1定位于细胞核，而翻译终止发生在细胞质中，这增加了OGFOD1在细胞核中具有其他功能的可能性。在本研究中，我们证明OGFOD1参与细胞周期调控。在MDA-MB-231乳腺癌细胞中敲低OGFOD1可显著阻碍细胞增殖，并通过降低G1/S期转换和G2/M期相关转录因子及其靶基因的mRNA水平，导致G1期和G2/M期细胞积累。我们还通过生物信息学分析和免疫组织化学证实OGFOD1在乳腺癌组织中高表达。因此，我们认为OGFOD1是乳腺癌细胞增殖所必需的，并且与乳腺癌的不良预后相关。
