title: RB and a novel E2F-1 binding protein in MHC class II deficient B-cell lines and normal IFN-gamma induction of the class IL transactivator CIITA in class II non-inducible RB-defective tumor lines.
abstract: The major histocompatibility (MHC) class II genes encode cell surface proteins that bind antigenic peptide for presentation to T-cells. The class II proteins are expressed constitutively on B-cells and EBV-transformed B-cells, and are inducible by IFN-gamma on a wide variety of cell types. Retinoblastoma protein (RB) is a tumor suppressor and functions as a transcriptional repressor by binding and inactivating the transactivator E2F-I. RB-defective tumor lines are non-inducible for MHC class II by IFN-gamma, or very weakly inducible, but transfection of 2 different lines with RB expression vectors re-establishes or substantially enhances class II inducibility. Therefore, we examined the RB status of a series of B-cell mutants that are defective in class II expression, generated either in vitro or derived from Bare Lymphocyte Syndrome (BLS) patients. Nuclear matrix-bound RB was detectable in all cases, indicating that loss of RB is not responsible for decreased class II expression in these lines. A second E2F-I binding protein, most likely DP-I, was also apparently normal in both class II-positive and -negative B-cell lines. We also examined the IFN-gamma induction of CIITA in RB-defective lines. CIITA is a class II gene transactivator known to be defective in one form of BLS and to be required for the induction of MHC class II by IFN-gamma. CIITA mRNA is normally inducible by IFN-gamma in class II non-inducible, RB-defective lines, and in one line, re-expression of RB has no effect on CIITA mRNA induction levels. Thus, the block in MHC class II inducibility in RB-defective cells is not due to a block in CIITA inducibility.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of South Florida College of Medicine, Tampa 33612, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Tschickardt
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: M
authors.initials: M
authors.lastname: Jacim
authors.forename: G D
authors.initials: GD
authors.lastname: Ussery
authors.forename: V
authors.initials: V
authors.lastname: Steimle
authors.forename: B
authors.initials: B
authors.lastname: Mach
authors.forename: G
authors.initials: G
authors.lastname: Blanck
mesh_terms: D034961:Antigens, Nuclear; D001402:B-Lymphocytes / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D034961:Antigens, Nuclear; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D000949:Histocompatibility Antigens Class II; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors; D007371:Interferon-gamma