title: Biochemical characterisation of the proteins encoded by the DiGeorge critical region 6 (DGCR6) genes.
abstract: The DiGeorge critical region 6 (DGCR6) gene exists in two highly homologous copies (DGCR6 and DGCR6L) on chromosome 22q11 and is deleted in patients with velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS). The DGCR6 mRNA levels are increased in metastatic mammary tumour cells and regulate the expression of neighbouring genes at the 22q11 region. Newly developed monoclonal antibodies detected predominantly nuclear phosphoproteins of approximately 25 kDa, with low expression levels in the cytoplasm. Both proteins have half-lives of about 2.5 h. Exogenously expressed DGCR6 and DGCR6L migrated with slightly different mobility in SDS-gels in accordance with two immunoreactive bands observed for the endogenous proteins. DGCR6 is found at low levels in primary human fibroblasts or peripheral blood mononuclear cells, while tumour cells, B-cells transformed by EBV as well as activated normal human T cells, contain elevated levels of the proteins. The proteins are differentially expressed in mammalian tissues, with high protein levels in heart, liver and skeletal muscle. These observations are important as some patients with DGCR6 syndrome exhibit a T-cell deficiency and/or cardiac malformations. As the DGCR6 protein(s) influence gene expression in trans, we analysed the influence of DGCR6/DGCR6L on the Epstein-Barr virus-encoded oncoproteins EBNA2 and EBNA3c in the activation of the viral LMP1 promoter, as well as LMP1-mediated activation of NFkB, but found no effect in either setting.
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene, Abteilung Virologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Pfuhl
authors.forename: Matthias
authors.initials: M
authors.lastname: Dürr
authors.forename: Andreas
authors.initials: A
authors.lastname: Spurk
authors.forename: Björn
authors.initials: B
authors.lastname: Schwalbert
authors.forename: Ruth
authors.initials: R
authors.lastname: Nord
authors.forename: Josef
authors.initials: J
authors.lastname: Mysliwietz
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Friedrich A
authors.initials: FA
authors.lastname: Grässer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes; D002892:Chromosomes, Human, Pair 22; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D006801:Humans; D008213:Lymphocyte Activation; D015674:Mammary Neoplasms, Animal; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; C101273:DGCR6 protein, human; D016326:Extracellular Matrix Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D011506:Proteins