JMJD4 promotes tumor progression via inhibition of the PDCD5-TP53 pathway
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Programmed cell death 5 (PDCD5) regulates cell death and suppressestumor progression. Since the stability and nuclear translocationof PDCD5 are regulated by TP53-dependent cell deathstimuli, knowledge of the regulatory mechanism of PDCD5function is required to better understand the TP53-signalingpathway. We identified Jumonji domain-containing protein 4(JMJD4) to be a PDCD5-interacting protein using liquid chromatography-mass spectrometry (LC-MS). Interestingly, JMJD4 upregulatescell proliferation and chemo-resistance under genotoxicstress conditions by colony-formation assay and decreasesTP53-related apoptotic genes (BAX, PUMA) by suppressing proteinlevels of PDCD5. Additionally, using the Cancer GenomeAtlas and the Gene Expression Omnibus database to confirmthe clinical correlation between JMJD4 and cancer patients,we verified that JMJD4 is associated with a poor prognosis incolon cancer and lung cancer patients. Therefore, this study demonstratesthat JMJD4 directly interacts with PDCD5, regulatescancer cell death negatively, and could be a potential therapeutictarget for cancer development.
Abstract
Programmed cell death 5 (PDCD5) regulates cell death and suppressestumor progression. Since the stability and nuclear translocationof PDCD5 are regulated by TP53-dependent cell deathstimuli, knowledge of the regulatory mechanism of PDCD5function is required to better understand the TP53-signalingpathway. We identified Jumonji domain-containing protein 4(JMJD4) to be a PDCD5-interacting protein using liquid chromatography-mass spectrometry (LC-MS). Interestingly, JMJD4 upregulatescell proliferation and chemo-resistance under genotoxicstress conditions by colony-formation assay and decreasesTP53-related apoptotic genes (BAX, PUMA) by suppressing proteinlevels of PDCD5. Additionally, using the Cancer GenomeAtlas and the Gene Expression Omnibus database to confirmthe clinical correlation between JMJD4 and cancer patients,we verified that JMJD4 is associated with a poor prognosis incolon cancer and lung cancer patients. Therefore, this study demonstratesthat JMJD4 directly interacts with PDCD5, regulatescancer cell death negatively, and could be a potential therapeutictarget for cancer development.