JMJD5

The dysregulated expression of cyclin genes can lead to the uncontrolled proliferation of cancer cells. Histone demethylase Jumonji-C domain-containing protein 5 (KDM8, JMJD5) and cyclin A1 (CCNA1) are pivotal in cell cycle progression. A promising candidate for augmenting cancer treatment is Allyl isothiocyanate (AITC), a natural dietary chemotherapeutic and epigenetic modulator. This study aimed to investigate AITC's impact on the KDM8/CCNA1 axis to elucidate its role in oral squamous cell carcinoma (OSCC) tumorigenesis...

Aberrant activation of epidermal growth factor receptor (EGFR) signaling is closely related to the development of non-small cell lung cancer (NSCLC). However, targeted EGFR therapeutics such as tyrosine kinase inhibitors (TKIs) face the challenge of EGFR mutation-mediated resistance. Here, we showed that the reduced JmjC domain-containing 5 (JMJD5) expression is negatively associated with EGFR stability and NSCLC progression. Mechanically, JMJD5 cooperated with E3 ligase HUWE1 to destabilize EGFR and EGFR TKI-resistant mutants for proteasomal degradation, thereby inhibiting NSCLC growth and promoting TKI sensitivity...

BACKGROUND: This study aimed to identify the specific T cell co-stimulatory and co-inhibitory factors that play prognostic roles in patients with glioblastoma. Additionally, the unique histone H3 modification enzymes that regulate the expression levels of these specific co-stimulatory and co-inhibitory factors were investigated. METHODS: The medical records of 84 patients newly diagnosed with glioblastoma at our institution from January 2006 to December 2020 were retrospectively reviewed...

Jumonji-C domain-containing protein 5 (JMJD5) is a 2-oxoglutarate (2OG)-dependent oxygenase that plays important roles in development, circadian rhythm, and cancer through unclear mechanisms. JMJD5 has been reported to have activity as a histone protease, as an N ε -methyl lysine demethylase, and as an arginine residue hydroxylase. Small-molecule JMJD5-selective inhibitors will be useful for investigating its (patho)physiological roles. Following the observation that the broad-spectrum 2OG oxygenase inhibitor pyridine-2,4-dicarboxylic acid (2,4-PDCA) is a 2OG-competing JMJD5 inhibitor, we report that 5-aminoalkyl-substituted 2,4-PDCA derivatives are potent JMJD5 inhibitors manifesting selectivity for JMJD5 over other human 2OG oxygenases...

Jumonji-C (JmjC) domain-containing protein 5 (JMJD5) is a human 2-oxoglutarate (2OG) and Fe(ii)-dependent oxygenase which catalyses the post-translational C3 hydroxylation of arginyl-residues and which is linked to the circadian rhythm and to cancer biology through as yet unidentified mechanisms. We report robust solid phase extraction coupled to mass spectrometry (SPE-MS)-based JMJD5 assays which enable kinetic and high-throughput inhibition studies. The kinetic studies reveal that some synthetic 2OG derivatives, notably including a 2OG derivative with a cyclic carbon backbone ( i...

Metabolic reprogramming is considered one of the main driving forces for tumor progression, providing energy and substrates of biosynthesis to support rapid neoplastic proliferation. Particularly, the tumor suppressor protein p53 was shown to revert the Warburg effect and play complex roles in regulating glucose metabolism. Jumonji C domain-containing protein 5 (JMJD5) has previously been reported as a negative regulator of p53. However, the role of JMJD5 in p53-mediated metabolic reprogramming remains elusive...

Although protein hydroxylation is a relatively poorly characterized posttranslational modification, it has received significant recent attention following seminal work uncovering its role in oxygen sensing and hypoxia biology. Although the fundamental importance of protein hydroxylases in biology is becoming clear, the biochemical targets and cellular functions often remain enigmatic. JMJD5 is a "JmjC-only" protein hydroxylase that is essential for murine embryonic development and viability. However, no germline variants in JmjC-only hydroxylases, including JMJD5, have yet been described that are associated with any human pathology...

JmjC (Jumonji-C) domain-containing 5 (JMJD5) plays important roles in circadian regulation in plants and humans and is involved in embryonic development and cell proliferation. JMJD5 is a 2-oxoglutarate (2OG) and Fe(II) dependent oxygenase of the JmjC subfamily, which includes histone Nε -methyl lysine-demethylases (KDMs) and hydroxylases catalysing formation of stable alcohol products. JMJD5 is reported to have KDM activity, but has been shown to catalyse C-3 hydroxylation of arginine residues in sequences from human regulator of chromosome condensation domain-containing protein 1 (RCCD1) and ribosomal protein S6 (RPS6) in vitro...

BACKGROUND: RNA-binding proteins (RBPs) and circular RNAs (circRNAs) play important roles in glioblastoma multiforme (GBM). Aerobic glycolysis is a metabolic characteristic of GBM. However, the roles of RBPs and circRNAs in aerobic glycolysis in GBM remain unclear. The aim of this study is to explore the mechanisms by which RBPs and circRNAs regulate aerobic glycolysis in GBM cells. METHODS: RNA sequencing and circRNA microarray analysis were performed to identify RBPs and circRNAs for further study...

The surreptitious discoveries of the protease activities on arginine-methylated targets of a subfamily of Jumonji domain-containing family including JMJD5, JMJD6, and JMJD7 pose several questions regarding their authenticity, function, purpose, and relations with others. At the same time, despite several decades of efforts and massive accumulating data regarding the roles of the arginine methyltransferase family (PRMTs), the exact function of this protein family still remains a mystery, though it seems to play critical roles in transcription regulation, including activation and inactivation of a large group of genes, as well as other biological activities...

Overexpression of cancer upregulated gene (CUG) 2 induces cancer stem cell-like phenotypes, such as enhanced epithelial-mesenchymal transition, sphere formation, and doxorubicin resistance. However, the precise mechanism of CUG2-induced oncogenesis remains unknown. We evaluated the effects of overexpression of CUG2 on microRNA levels using a microRNA microarray. Levels of miR-3656 were decreased when CUG2 was overexpressed; on the basis of this result, we further examined the target proteins of this microRNA...

Background : JumonjiC (JmjC) domain-containing protein 5 ( JMJD5 ) plays an important part in cancer metabolism. However, the prognostic value of JMJD5 in most human cancers is unknown yet. We aimed to examine the expression level and prognostic value of JMJD5 , immune cell infiltration in cancer patients, and simultaneously to examine the correlations among them. Materials and methods : The mRNA and protein expression of JMJD5 were analyzed through online Tumor Immune Estimation Resource (TIMER) or immunohistochemistry (IHC) of tissue microarray sections (TMAs) in cancer versus normal tissues...

Proteins in Jumonji family function as histone demethylases and participate in cardiac development. Jumonji domain containing 5 (JMJD5) is responsible for the embryonic development through removing methyl moieties from H3K36me2 histone, and has pro-proliferative effect on heart and eye development. However, the protective role of JMJD5 against oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury in cardiomyocytes has not been fully understood. Firstly, myocardial ischemia/reperfusion (I/R) rat model was established by ligation of left coronary artery...

More than 30% of genes in higher eukaryotes are regulated by RNA polymerase II (Pol II) promoter proximal pausing. Pausing is released by the positive transcription elongation factor complex (P-TEFb). However, the exact mechanism by which this occurs and whether phosphorylation of the carboxyl-terminal domain of Pol II is involved in the process remains unknown. We previously reported that JMJD5 could generate tailless nucleosomes at position +1 from transcription start sites (TSS), thus perhaps enable progression of Pol II...

Dysregulation of histone demethylase Jumonji-C domain-containing protein 5 (JMJD5) has been identified as a great effect on tumorigenesis. Silibinin is a commonly used anti-hepatotoxic drug and exhibits anticancer effect in various cancers. However, the antitumor mechanism between silibinin and JMJD5 in oral squamous cell carcinoma (OSCC) remains unclear. In this study, the clinical significance of JMJD5 on OSCC patients was assessed through tissue microarray. Furthermore, mice bearing patient-derived tumor xenografts (PDTXs) and tongue cancer cell lines were treated with silibinin and evaluated for tumor growth and JMJD5 expression...

A majority of infant and pediatric leukemias are caused by the mixed-lineage leukemia gene (MLL) fused with a variety of candidates. Several underlying mechanisms have been proposed. One currently popular view is that truncated MLL1 fusion and its associated complex constitutively hijacks super elongation complex, including positive transcription elongation factor b, CDK9, and cyclin T1 complex and DOT1L, to enhance the expression of transcription factors that maintain or restore stemness of leukocytes, as well as prevent the differentiation of hematopoietic progenitor cells...

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Lumen integrity in vascularization requires fully differentiated endothelial cells (ECs). Here, we report that endothelial-mesenchymal transitions (EndMTs) emerged in ECs of cerebral arteriovenous malformation (AVMs) and caused disruption of the lumen or lumen disorder. We show that excessive Sry-box 2 (Sox2) signaling was responsible for the EndMTs in cerebral AVMs. EC-specific suppression of Sox2 normalized endothelial differentiation and lumen formation and improved the cerebral AVMs. Epigenetic studies showed that induction of Sox2 altered the cerebral-endothelial transcriptional landscape and identified jumonji domain-containing protein 5 (JMJD5) as a direct target of Sox2...

Jumonji C domain-containing (JMJD) proteins are mostly epigenetic regulators that demethylate histones. However, a hitherto neglected subfamily of JMJD proteins, evolutionarily distant and characterized by their relatively small molecular weight, exerts different functions by hydroxylating proteins and RNA. Recently, unsuspected proteolytic and tyrosine kinase activities were also ascribed to some of these small JMJD proteins, further increasing their enzymatic versatility. Here, we discuss the ten human small JMJD proteins (HIF1AN, HSPBAP1, JMJD4, JMJD5, JMJD6, JMJD7, JMJD8, RIOX1, RIOX2, TYW5) and their diverse physiological functions...

The circadian system ensures that plants respond appropriately to environmental change by predicting regular transitions that occur during diel cycles. In order to be most useful, the circadian system needs to be compensated against daily and seasonal changes in temperature that would otherwise alter the pace of this biological oscillator. We demonstrate that an evening-phased protein, the putative histone demethylase JMJD5, contributes to temperature compensation. JMJD5 is co-expressed with components of the Evening Complex, an agglomeration of proteins including EARLY FLOWERING3 (ELF3), ELF4, and LUX ARRHYTHYMO (LUX), which also integrates temperature changes into the molecular clockwork...