Altered binding of regulatory factors to HLA class I enhancer sequence in human tumor cell lines lacking class I antigen expression
| Autor: | Philippe Kourilsky, Pascale Paul, Helene Zinszner, Odile Blanchet, Jean Dausset, Jean-François Bourge, Laurent Degos, Alain Israel |
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| Rok vydání: | 1992 |
| Předmět: |
CD74
Molecular Sequence Data CD1 Gene Expression Genes MHC Class I Human leukocyte antigen Cell Line Neoplasms MHC class I Humans RNA Messenger Multidisciplinary Base Sequence biology Antigen processing Cell Membrane Histocompatibility Antigens Class I MHC Class I Gene NF-kappa B Antibodies Monoclonal NF-kappa B p50 Subunit Transporter associated with antigen processing MHC restriction Molecular biology DNA-Binding Proteins Enhancer Elements Genetic biology.protein Female DNA Probes Oligonucleotide Probes Protein Binding Transcription Factors Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 89:3488-3492 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Class I antigens encoded in the major histocompatibility complex (MHC) (HLA in man, H-2 in the mouse) play a key role in the recognition of target cells by cytolytic T lymphocytes. Tumor cells frequently do not express class I MHC molecules, which strongly suggests that down-regulation of the latter facilitates escape of tumor cells from immune surveillance. The expression of class I MHC genes is tightly regulated. An enhancer element, conserved in the promoters of mouse and human MHC genes, has been shown to be important for mouse class I MHC gene expression. At least two related regulatory factors (KBF1 and NF-kappa B) bind to this regulatory element. We have analyzed the binding of these factors in cellular extracts of 23 human tumor cell lines displaying various levels of class I mRNA and surface expression. In this panel, combined deficiency of KBF1- and NF-kappa B-like DNA-binding activities was frequent among the class I-negative cell lines and correlated with the absence of class I mRNA. A few cell lines that lack KBF1 binding activity still display NF-kappa B-like activity and express normal levels of MHC class I mRNA. These results suggest (i) that, in the absence of KBF1, NF-kappa B or a related factor promotes MHC class I gene transcription; and (ii) that a combined defect in KBF1/NF-kappa B DNA-binding activity can cause a pleiotropic defect in class I gene expression, which may facilitate tumor progression. |
| Databáze: | OpenAIRE |
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