title: Proteomic changes induced by histone demethylase JMJD3 in TNF alpha-treated human monocytic (THP-1) cells.
abstract: JMJD3, a Jumonji C family histone demethylase, plays an important role in the regulation of inflammation induced by the transcription factor nuclear factor-kappa B (NF-κB) in response to various stimuli. JMJD3 is a histone-3 lysine-27 trimethylation (H3K27me3) demethylase, a histone mark associated with transcriptional repression and activation of a diverse set of genes. The present study assessed stable JMJD3 knockdown (KD)-dependent proteomic profiling in human leukemia monocyte (THP-1) cells to analyze the JMJD3-mediated differential changes of marker expression in inflammatory cells. To analyze the protein expression profile of tumor necrosis factor-alpha (TNF-α)-stimulated JMJD3-kd THP-1 cells, we employed matrix-assisted-laser-desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Additionally, Ingenuity Pathways Analysis (IPA) was applied to establish the molecular networks. A comparative proteomic profile was determined in TNF-α-treated both of JMJD3-kd THP-1 cells and THP-1 scrambled (sc) cells. The expression of tripartite motif protein (TRIM5), glutathione peroxidase (GPx), glia maturation factor-γ (GMFG), caspase recruitment domain family, member 14 (CARMA2), and dUTP pyrophosphatase were significantly down-regulated, whereas heat shock protein beta-1 (HspB1) and prohibition were significantly up-regulated in JMJD3-kd THP-1 cells. The molecular and signaling networks of the differentially expressed proteins in JMJD3-kd THP-1 cells were determined by IPA. The molecular network signatures and functional proteomics obtained in this study may facilitate the suppression of different key inflammatory regulators through JMJD3-attenuation, which would be crucial to evaluate potential therapeutic targets and to elucidate the molecular mechanism of JMJD3-kd dependent effects in THP-1 cells.
authors.affiliation: Department of Molecular & Life Science, Hanyang University, Ansan, Republic of Korea. amitabhdas.kn@gmail.com
authors.forename: Amitabh
authors.initials: A
authors.lastname: Das
authors.forename: Nando Dulal
authors.initials: ND
authors.lastname: Das
authors.forename: Kyoung Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Hyung Tae
authors.initials: HT
authors.lastname: Lee
authors.forename: DalMuri
authors.initials: D
authors.lastname: Han
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Choi
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Kang
authors.forename: Young Gyu
authors.initials: YG
authors.lastname: Chai
mesh_terms: D000090103:Antiviral Restriction Factors; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C512648:NUDC protein, human; D009687:Nuclear Proteins; D020543:Proteome; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases