| JMJD4 promotes tumor progression via inhibition of the PDCD5–TP53 pathway |
Hyunsik Kim1 (Graduate Student), Soo-Yeon Park1 (Research Assistant Professor), Soo Yeon Lee1 (Research Assistant Professor), Jae-Hwan Kwon1 (Graduate Student), Seunghee Byun1 (Graduate Student), Mi Jeong Kim2 (Research Assistant Professor), Sungryul Yu3 (Associate Professor), Jung-Yoon Yoo  4,# (Associate Professor), Ho-Geun Yoon 1,*,# (Professor) |
1Department of Biochemistry and Molecular Biology, Severance Medical Research Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine,
2Department of Food and Biotechnology, College of Science and Technology Institute of Natural Sciences Korea University,
3Department of Clinical Laboratory Science, Semyung University,
4Department of Biomedical Laboratory Science, Yonsei University MIRAE Campus |
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Abstract
Programmed cell death 5 (PDCD5) regulates cell death and suppresses tumor progression. Since the stability and nuclear translocation of PDCD5 are regulated by TP53-dependent cell death stimuli, knowledge of the regulatory mechanism of PDCD5 function is required to better understand the TP53-signaling pathway. We identified Jumonji domain–containing protein 4 (JMJD4) to be a PDCD5-interacting protein using liquid chromatography–mass spectrometry (LC-MS). Interestingly, JMJD4 upregulates cell proliferation and chemo-resistance under genotoxic stress conditions by colony-formation assay and decreases TP53-related apoptotic genes (BAX, PUMA) by suppressing protein levels of PDCD5. Additionally, using the Cancer Genome Atlas and the Gene Expression Omnibus database to confirm the clinical correlation between JMJD4 and cancer patients, we verified that JMJD4 is associated with a poor prognosis in colon cancer and lung cancer patients. Therefore, this study demonstrates that JMJD4 directly interacts with PDCD5, regulates cancer cell death negatively, and could be a potential therapeutic target for cancer development.
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| Abstract, Accepted Manuscript(in press) [Submitted on November 15, 2022, Accepted on December 27, 2022] |
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