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PMID: 8496683 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

KBF1 (p50 NF-kappa B homodimer) acts as a repressor of H-2Kb gene expression in metastatic tumor cells.

The Journal of experimental medicine ·Vol. 177 ·No. 6 ·1993-06-01 ·Pages 1651-62

Plaksin D, Baeuerle PA, Eisenbach L

Abstract

Downregulation of major histocompatibility complex class I expression is causally related to high malignancy and low immunogenicity of certain murine tumors. In this study, we have analyzed the roles of the nuclear factors KBF1/p50 and p65 in regulation of class I expression in high and low metastatic tumor cells. Low class I-expressing cells show at higher levels of KBF1/p50 and NF-kappa B (p50/p65) binding activity than high class I-expressing cells. However, an excess of KBF1 over NF-kappa B is observed in low expressing cells, while an excess of NF-kappa B over KBF1 is observed in high expressing cells. Stable transfection of a p65 expression vector into low class I-expressing cells activated H-2 transcription and cell surface expression, while stable transfection of p50 expression vector into high expressing cells suppressed H-2Kb transcription and cell surface expression. Our studies suggest that KBF1 has the potential of downregulating class I gene expression, whereas dimers containing the p65 subunit are activators of class I gene expression.

Related Genes
H-2K<up>b</up>
MeSH Terms
Animals DNA-Binding Proteins/analysis Enhancer Elements, Genetic Gene Expression Regulation, Neoplastic H-2 Antigens/genetics Lung Neoplasms/genetics Mice Mice, Inbred C57BL NF-kappa B/metabolism NF-kappa B p50 Subunit Neoplasm Metastasis/genetics Promoter Regions, Genetic Repressor Proteins/physiology Transcription Factors/physiology Tumor Cells, Cultured
Chemicals
DNA-Binding Proteins H-2 Antigens H-2Kb protein, mouse NF-kappa B NF-kappa B p50 Subunit NFKB1 protein, human Repressor Proteins Transcription Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Plaksin D
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Baeuerle P A
Eisenbach L
References (80)
80 references, click to expand
  1. Antigen presentation: structural themes and functional variations.
    Immunol Today. 1991 Apr;12(4):124-9 PMID: 1711855
  2. DNA sequence analysis of the C3H H-2Kk and H-2Dk loci. Evolutionary relationships to H-2 genes from four other mouse strains.
    J Immunol. 1987 Dec 1;139(11):3878-85 PMID: 3680952
  3. Selective changes in expression of HLA class I polymorphic determinants in human solid tumors.
    Proc Natl Acad Sci U S A. 1989 Sep;86(17):6719-23 PMID: 2672003
  4. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression.
    J Immunol. 1981 Jan;126(1):317-21 PMID: 6935293
  5. Altered binding of regulatory factors to HLA class I enhancer sequence in human tumor cell lines lacking class I antigen expression.
    Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3488-92 PMID: 1565643
  6. Detailed analysis of the mouse H-2Kb promoter: enhancer-like sequences and their role in the regulation of class I gene expression.
    Cell. 1986 Jan 31;44(2):261-72 PMID: 3510743
  7. The role of the p50 and p65 subunits of NF-kappa B in the recognition of cognate sequences.
    New Biol. 1991 Mar;3(3):279-88 PMID: 1878350
  8. Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal.
    Cell. 1990 Sep 7;62(5):1019-29 PMID: 2203532
  9. Presentation of antigenic peptides by MHC class I molecules.
    Trends Cell Biol. 1992 Jul;2(7):202-7 PMID: 14731501
  10. H-2-restricted cytolytic T cells specific for HLA can recognize a synthetic HLA peptide.
    Nature. 1986 Dec 11-17;324(6097):578-9 PMID: 3491326
  11. Resistance to cell-mediated cytotoxicity is correlated with reduction of H-2K gene products in AKR leukemia.
    Immunogenetics. 1982;16(3):257-64 PMID: 6982849
  12. Transcriptional regulation of the HIV-1 promoter by NF-kappa B in vitro.
    Genes Dev. 1992 May;6(5):761-74 PMID: 1577271
  13. The NF-kappa B p50 precursor, p105, contains an internal I kappa B-like inhibitor that preferentially inhibits p50.
    EMBO J. 1992 Aug;11(8):3003-9 PMID: 1639070
  14. Purification of KBF1, a common factor binding to both H-2 and beta 2-microglobulin enhancers.
    EMBO J. 1987 Nov;6(11):3317-24 PMID: 3322806
  15. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides.
    Cell. 1986 Mar 28;44(6):959-68 PMID: 2420472
  16. Selective loss of HLA-A,B,C locus products in colorectal adenocarcinoma.
    Lancet. 1988 Apr 9;1(8589):823-4 PMID: 2895339
  17. Reversal of the metastatic phenotype in Lewis lung carcinoma cells after transfection with syngeneic H-2Kb gene.
    Proc Natl Acad Sci U S A. 1988 Jun;85(12):4463-7 PMID: 3380801
  18. Down-regulation of class I HLA antigens and of the Epstein-Barr virus-encoded latent membrane protein in Burkitt lymphoma lines.
    Proc Natl Acad Sci U S A. 1987 Jul;84(13):4567-71 PMID: 3037521
  19. The DNA binding subunit of NF-kappa B is identical to factor KBF1 and homologous to the rel oncogene product.
    Cell. 1990 Sep 7;62(5):1007-18 PMID: 2203531
  20. NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats.
    Trends Biochem Sci. 1992 Apr;17(4):135-40 PMID: 1533967
  21. TNF stimulates expression of mouse MHC class I genes by inducing an NF kappa B-like enhancer binding activity which displaces constitutive factors.
    EMBO J. 1989 Dec 1;8(12):3793-800 PMID: 2555174
  22. The p65 subunit is responsible for the strong transcription activating potential of NF-kappa B.
    EMBO J. 1991 Dec;10(12):3805-17 PMID: 1935902
  23. The candidate oncoprotein Bcl-3 is an antagonist of p50/NF-kappa B-mediated inhibition.
    Nature. 1992 Sep 24;359(6393):339-42 PMID: 1406939
  24. Binding of a nuclear factor to a regulatory sequence in the promoter of the mouse H-2Kb class I major histocompatibility gene.
    Mol Cell Biol. 1987 Jan;7(1):305-13 PMID: 3561391
  25. Intramolecular masking of the nuclear location signal and dimerization domain in the precursor for the p50 NF-kappa B subunit.
    Cell. 1992 Mar 20;68(6):1121-33 PMID: 1547506
  26. I kappa B: a specific inhibitor of the NF-kappa B transcription factor.
    Science. 1988 Oct 28;242(4878):540-6 PMID: 3140380
  27. Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells.
    Nature. 1983 Oct 27-Nov 2;305(5937):771-5 PMID: 6355856
  28. Activity of the kappa B enhancer of the interleukin-2 receptor alpha chain in somatic cell hybrids is accompanied by the nuclear localization of NF-kappa B.
    New Biol. 1991 Nov;3(11):1097-105 PMID: 1777483
  29. Regulation of murine class I genes by interferons is controlled by regions located both 5' and 3' to the transcription initiation site.
    Proc Natl Acad Sci U S A. 1987 May;84(10):3380-4 PMID: 3106967
  30. Expression of a preproinsulin-beta-galactosidase gene fusion in mammalian cells.
    Proc Natl Acad Sci U S A. 1983 Sep;80(17):5198-202 PMID: 6310564
  31. Interferon response sequence potentiates activity of an enhancer in the promoter region of a mouse H-2 gene.
    Nature. 1986 Aug 21-27;322(6081):743-6 PMID: 3748155
  32. A 65-kappaD subunit of active NF-kappaB is required for inhibition of NF-kappaB by I kappaB.
    Genes Dev. 1989 Nov;3(11):1689-98 PMID: 2691328
  33. The inducible transcription activator NF-kappa B: regulation by distinct protein subunits.
    Biochim Biophys Acta. 1991 Apr 16;1072(1):63-80 PMID: 2018779
  34. DNA binding and I kappa B inhibition of the cloned p65 subunit of NF-kappa B, a rel-related polypeptide.
    Cell. 1991 Mar 8;64(5):961-9 PMID: 2001591
  35. MHC imbalance and metastatic spread in Lewis lung carcinoma clones.
    Int J Cancer. 1983 Jul 15;32(1):113-20 PMID: 6862690
  36. The characterization of the promoter of the gene encoding the p50 subunit of NF-kappa B indicates that it participates in its own regulation.
    EMBO J. 1992 Jan;11(1):195-203 PMID: 1740105
  37. Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer.
    J Exp Med. 1985 May 1;161(5):1135-51 PMID: 2580935
  38. Regulation of HLA class I transcription in T cells.
    J Immunol. 1989 Nov 15;143(10):3385-9 PMID: 2809207
  39. Cloning of an NF-kappa B subunit which stimulates HIV transcription in synergy with p65.
    Nature. 1991 Aug 22;352(6337):733-6 PMID: 1876189
  40. Differential expression of H-2 gene products in tumour cells in associated with their metastatogenic properties.
    Nature. 1980 Nov 13;288(5787):179-81 PMID: 7432518
  41. Expression of HLA-A,B,C antigens on primary and metastatic tumor cell populations of human carcinomas.
    Cancer Res. 1991 Dec 1;51(23 Pt 1):6372-80 PMID: 1933900
  42. Loss of expression of transplantation antigens encoded by the H-2K locus on Lewis lung carcinoma cells and its relevance to the tumor's metastatic properties.
    J Natl Cancer Inst. 1983 Jul;71(1):139-45 PMID: 6345878
  43. Functional expression of a mouse H-2Kb gene isolated from non-expressing teratocarcinoma cells.
    EMBO J. 1984 Mar;3(3):597-601 PMID: 6714227
  44. The SV40 TC-II(kappa B) enhanson binds ubiquitous and cell type specifically inducible nuclear proteins from lymphoid and non-lymphoid cell lines.
    EMBO J. 1989 Dec 20;8(13):4215-27 PMID: 2556265
  45. Regulation of gene expression by interferons: control of H-2 promoter responses.
    Science. 1988 Mar 11;239(4845):1302-6 PMID: 3125612
  46. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B.
    Science. 1991 Mar 22;251(5000):1490-3 PMID: 2006423
  47. Developmental and tissue-specific expression of nuclear proteins that bind the regulatory element of the major histocompatibility complex class I gene.
    J Exp Med. 1989 Apr 1;169(4):1309-21 PMID: 2926327
  48. Striking paucity of HLA-A, B, C and beta 2-microglobulin on human neuroblastoma cell lines.
    J Immunol. 1983 May;130(5):2471-8 PMID: 6187860
  49. I kappa B gamma, a 70 kd protein identical to the C-terminal half of p110 NF-kappa B: a new member of the I kappa B family.
    Cell. 1992 Mar 20;68(6):1109-20 PMID: 1339305
  50. Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity.
    Nature. 1983 Oct 27-Nov 2;305(5937):776-9 PMID: 6605479
  51. Retinoic acid-dependent transactivation of major histocompatibility complex class I promoters by the nuclear hormone receptor H-2RIIBP in undifferentiated embryonal carcinoma cells.
    Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):937-41 PMID: 1736309
  52. Two transcription factors, NF-kappa B and H2TF1, interact with a single regulatory sequence in the class I major histocompatibility complex promoter.
    Proc Natl Acad Sci U S A. 1988 Feb;85(3):723-7 PMID: 3422454
  53. A common positive trans-acting factor binds to enhancer sequences in the promoters of mouse H-2 and beta 2-microglobulin genes.
    Proc Natl Acad Sci U S A. 1987 May;84(9):2653-7 PMID: 3554244
  54. The SV40 TC-II(kappa B) and the related H-2Kb enhansons exhibit different cell type specific and inducible proto-enhancer activities, but the SV40 core sequence and the AP-2 binding site have no enhanson properties.
    EMBO J. 1989 Dec 20;8(13):4205-14 PMID: 2556264
  55. NF-kappa B contacts DNA by a heterodimer of the p50 and p65 subunit.
    EMBO J. 1991 Jul;10(7):1817-25 PMID: 2050119
  56. c-fos transfection of 3LL tumor cells turns on MHC gene expression and consequently reduces their metastatic competence.
    Int J Cancer. 1990 Jun 15;45(6):1131-6 PMID: 2351488
  57. A transcription factor interacting with the class I gene enhancer is inactive in tumorigenic cell lines which suppress major histocompatibility complex class I genes.
    Mol Cell Biol. 1990 Aug;10(8):4100-9 PMID: 2196446
  58. The c-fos proto-oncogene in murine 3LL carcinoma clones controls the expression of MHC genes.
    Oncogene. 1988 Feb;2(2):119-27 PMID: 2453011
  59. Many transcription factors interact synergistically with steroid receptors.
    Science. 1988 Dec 9;242(4884):1418-20 PMID: 3201230
  60. Absence of human leukocyte antigen molecules in skin tumors and some cutaneous appendages: evidence using monoclonal antibodies.
    J Am Acad Dermatol. 1983 Dec;9(6):867-71 PMID: 6196384
  61. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells.
    Nucleic Acids Res. 1989 Aug 11;17(15):6419 PMID: 2771659
  62. Major histocompatibility complex class I genes in murine fibrosarcoma IC9 are down regulated at the level of the chromatin structure.
    Mol Cell Biol. 1989 Jul;9(7):3136-42 PMID: 2506438
  63. Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity.
    Cell. 1991 Jun 28;65(7):1281-9 PMID: 1829648
  64. Molecular cloning of an enhancer binding protein: isolation by screening of an expression library with a recognition site DNA.
    Cell. 1988 Feb 12;52(3):415-23 PMID: 2964277
  65. The nucleotide sequence of the rat cytoplasmic beta-actin gene.
    Nucleic Acids Res. 1983 Mar 25;11(6):1759-71 PMID: 6300777
  66. Functional analysis of the mouse H-2Kb gene promoter in embryonal carcinoma cells.
    Immunogenetics. 1985;21(6):601-11 PMID: 2989166
  67. Loss of polymorphic A and B locus HLA antigens in colon carcinoma.
    Br J Cancer. 1988 Apr;57(4):374-7 PMID: 3291922
  68. Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B.
    Mol Cell Biol. 1990 Apr;10(4):1498-506 PMID: 2181276
  69. H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element.
    Proc Natl Acad Sci U S A. 1989 Nov;86(21):8289-93 PMID: 2554307
  70. Selective loss of HLA-A or HLA-B antigen expression in colon carcinoma.
    J Immunol. 1989 Jan 1;142(1):352-8 PMID: 2462591
  71. H-2Db gene transfer into highly metastatic D122 cells results in tumor rejection in allogeneic recipients, but does not affect metastasis in syngeneic recipients. Implications for mechanisms of allorejection.
    Int J Cancer. 1992 Nov 11;52(5):771-7 PMID: 1428231
  72. DNA binding of regulatory factors interacting with MHC-class-I gene enhancer correlates with MHC-class-I transcriptional level in class-I-defective cell lines.
    Int J Cancer Suppl. 1991;6:138-45 PMID: 1906051
  73. Two purified factors bind to the same sequence in the enhancer of mouse MHC class I genes: one of them is a positive regulator induced upon differentiation of teratocarcinoma cells.
    Nucleic Acids Res. 1989 Jul 11;17(13):5245-57 PMID: 2668878
  74. Independent modes of transcriptional activation by the p50 and p65 subunits of NF-kappa B.
    Genes Dev. 1992 May;6(5):775-87 PMID: 1577272
  75. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  76. Nuclear uptake control of NF-kappa B by MAD-3, an I kappa B protein present in the nucleus.
    EMBO J. 1993 Jan;12(1):201-11 PMID: 7679069
  77. The differential expression of H-2K versus H-2D antigens, distinguishing high-metastatic from low-metastatic clones, is correlated with the immunogenic properties of the tumor cells.
    Int J Cancer. 1984 Oct 15;34(4):567-73 PMID: 6490207
  78. NF-kappa B subunit regulation in nontransformed CD4+ T lymphocytes.
    Science. 1992 Jun 5;256(5062):1452-6 PMID: 1604322
  79. HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas.
    Br J Cancer. 1989 Feb;59(2):221-6 PMID: 2649129
  80. Identification of sequences responsible for positive and negative regulation by E1A in the promoter of H-2Kbm1 class I MHC gene.
    EMBO J. 1990 Jan;9(1):127-35 PMID: 2136829
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.177.6.1651
Published
1993-06-01
Pages
1651-62
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191052
Subset
IM
Grants
NCI NIH HHS · CA-28139 · United States
External Links
PubMed source DOI: 10.1084/jem.177.6.1651 PMC Full Text View journal details
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