title: Characterization of ZC3H15 as a potential TRAF-2-interacting protein implicated in the NFκB pathway and overexpressed in AML.
abstract: The gene product of the zinc finger CCCH-type containing 15 (ZC3H15) gene, an immediate early erythropoietin response gene (synonymous: LEREPO4), was further characterized. ZC3H15 was expressed ubiquitously in all human tissues tested by northern blotting and showed mainly a diffuse cytoplasmic distribution by immune fluorescence microscopy and western blotting of subcellular protein fractions. The expression of ZC3H15 was downregulated effectively in HeLa cells to ≤13% of the control by transfection of specific small interfering RNA (siRNA). Subsequent Affymetrix microarray analysis revealed 202 differentially expressed genes including 114 induced (≥3-fold) genes and 88 suppressed (≤0.3-fold) genes. The gene ontology (GO) categories containing an over-representation of differentially expressed genes comprised cell growth, transcription, cell adhesion, regulation of NF-κB, regulation of MAPK, cell cycle arrest and immune response. ZC3H15 interacted with the signaling adapter protein tumor necrosis factor receptor associated factor 2 (TRAF-2) as shown by co-immunoprecipitation. ZC3H15 expression was found to be significantly increased in acute myeloid leukemia (AML) samples compared to MDS, CML, ALL and normal bone marrow samples using the Leukemia Gene Atlas (LGA) database. Based on these data, it is hypothesized that ZC3H15 may interact with TRAF-2 functionally within the NF-κB pathway, and may be explored as a potential target in AML.
authors.affiliation: Department of Hematology/Oncology and Infectious Diseases, J.W. Goethe-University Hospital, 60595 Frankfurt/Main, Germany.
authors.forename: Gianni
authors.initials: G
authors.lastname: Capalbo
authors.forename: Thea
authors.initials: T
authors.lastname: Mueller-Kuller
authors.forename: Steffen
authors.initials: S
authors.lastname: Koschmieder
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Klein
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Urban J
authors.initials: UJ
authors.lastname: Scheuring
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D016328:NF-kappa B; D016601:RNA-Binding Proteins; D047992:TNF Receptor-Associated Factor 2; C583533:ZC3H15 protein, human