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PMID: 11992002 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

RelB-p50 NF-kappa B complexes are selectively induced by cytomegalovirus immediate-early protein 1: differential regulation of Bcl-x(L) promoter activity by NF-kappa B family members.

Journal of virology ·Vol. 76 ·No. 11 ·2002-06-00 ·Pages 5737-47

Jiang HY, Petrovas C, Sonenshein GE

Abstract

The NF-kappa B/Rel family has been implicated in control of transcription of the Bcl-x(L) gene, a target which mediates cell survival signals. The cytomegalovirus (CMV) immediate-early protein 1 (IE1) was previously shown to induce NF-kappa B activity. Here, we report that in both vascular smooth muscle cells (SMCs) and NIH 3T3 cells, surprisingly, IE1 failed to induce Bcl-x(L) promoter activity, although it induced activity of E8-CAT, a reporter construct driven by two copies of the NF-kappa B element upstream of the c-myc promoter (upstream regulatory element [URE]). Thus, the subunit nature of the NF-kappa B/Rel factors induced by IE1 was examined using immunofluorescence and immunoblotting. IE1 was found to selectively induce nuclear RelB and p50 in SMCs and NIH 3T3 cells. An increase in RelB protein mediated by IE1 could, in part, be related to an increase in steady-state relB mRNA levels. Consistent with this subunit identification, IE1 was unable to induce E8-CAT activity in relB(-/-) murine embryonic fibroblast cells. In cotransfection analysis of SMCs and NIH 3T3 cells, RelB and p50 proteins failed to induce Bcl-x(L) promoter activity while inducing E8-CAT. Furthermore, the NF-kappa B element of the Bcl-x(L) promoter only weakly bound RelB-p50 complexes compared to the URE NF-kappa B element. Overall, these findings demonstrate in SMCs and NIH 3T3 cells that the CMV IE1 protein selectively induces RelB and p50, which fail to activate the Bcl-x(L) promoter, indicating a strong specificity of binding and activity for the RelB member of the NF-kappa B family. Furthermore, our results implicate RelB in CMV infection of cells such as vascular SMCs.

MeSH Terms
3T3 Cells Animals Cattle Cell Nucleus/metabolism Cells, Cultured Chloramphenicol O-Acetyltransferase/genetics Cytomegalovirus/metabolism Female Genes, Reporter Humans Immediate-Early Proteins/metabolism Mice Muscle, Smooth, Vascular/cytology NF-kappa B/antagonists & inhibitors,metabolism NF-kappa B p50 Subunit Promoter Regions, Genetic Proto-Oncogene Proteins/genetics,metabolism Proto-Oncogene Proteins c-bcl-2/genetics Transcription Factor RelB Transcription Factors/genetics,metabolism Transcriptional Activation Viral Proteins bcl-X Protein
Chemicals
BCL2L1 protein, human Bcl2l1 protein, mouse IE1 protein, cytomegalovirus Immediate-Early Proteins NF-kappa B NF-kappa B p50 Subunit Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 RELB protein, human Relb protein, mouse Transcription Factors Viral Proteins bcl-X Protein Transcription Factor RelB Chloramphenicol O-Acetyltransferase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Jiang H Y
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118-2394, USA.
Petrovas Constantinos
Sonenshein Gail E
References (65)
65 references, click to expand
  1. TGF beta 1 inhibits NF-kappa B/Rel activity inducing apoptosis of B cells: transcriptional activation of I kappa B alpha.
    Immunity. 1996 Jul;5(1):31-40 PMID: 8758892
  2. Cell density and estradiol modulation of procollagen type III in cultured calf smooth muscle cells.
    J Biol Chem. 1982 Oct 25;257(20):12252-6 PMID: 7118942
  3. Trans activation of plasmid-borne promoters by adenovirus and several herpes group viruses.
    Nucleic Acids Res. 1984 Aug 10;12(15):5969-78 PMID: 6089105
  4. Trans activation of transcription by herpes virus products: requirement for two HSV-1 immediate-early polypeptides for maximum activity.
    EMBO J. 1984 Dec 20;3(13):3135-41 PMID: 6098466
  5. Human cytomegalovirus ie1 transactivates the alpha promoter-enhancer via an 18-base-pair repeat element.
    J Virol. 1989 Mar;63(3):1435-40 PMID: 2536844
  6. Heparin prevents vascular smooth muscle cell progression through the G1 phase of the cell cycle.
    J Biol Chem. 1989 Apr 25;264(12):6990-5 PMID: 2651437
  7. NF-kappa B activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation.
    EMBO J. 1989 Dec 20;8(13):4251-8 PMID: 2556267
  8. Interaction of an NF-kappa B-like factor with a site upstream of the c-myc promoter.
    Proc Natl Acad Sci U S A. 1990 Jun;87(12):4727-31 PMID: 2191300
  9. Expression of the c-myb proto-oncogene in bovine vascular smooth muscle cells.
    J Biol Chem. 1992 Mar 5;267(7):4625-30 PMID: 1537845
  10. NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats.
    Trends Biochem Sci. 1992 Apr;17(4):135-40 PMID: 1533967
  11. Human cytomegalovirus in a SCID-hu mouse: thymic epithelial cells are prominent targets of viral replication.
    Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):104-8 PMID: 7678330
  12. The c-rel protooncogene product represses NF-kappa B p65-mediated transcriptional activation of the long terminal repeat of type 1 human immunodeficiency virus.
    Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1023-7 PMID: 8430069
  13. NF-kappa B and Rel: participants in a multiform transcriptional regulatory system.
    Int Rev Cytol. 1993;143:1-62 PMID: 8449662
  14. The inducible transcription factor NF-kappa B: structure-function relationship of its protein subunits.
    Biochem J. 1993 Mar 1;290 ( Pt 2):297-308 PMID: 8452515
  15. Cytomegalovirus infection enhances smooth muscle cell proliferation and intimal thickening of rat aortic allografts.
    J Clin Invest. 1993 Aug;92(2):549-58 PMID: 8394384
  16. Transcriptional regulation of human polyomavirus JC: evidence for a functional interaction between RelA (p65) and the Y-box-binding protein, YB-1.
    J Virol. 1996 Sep;70(9):5944-53 PMID: 8709216
  17. 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
  18. 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
  19. 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
  20. The inducible transcription activator NF-kappa B: regulation by distinct protein subunits.
    Biochim Biophys Acta. 1991 Apr 16;1072(1):63-80 PMID: 2018779
  21. Contribution of NF-kappa B and Sp1 binding motifs to the replicative capacity of human immunodeficiency virus type 1: distinct patterns of viral growth are determined by T-cell types.
    J Virol. 1991 Aug;65(8):4350-8 PMID: 2072454
  22. RelB, a new Rel family transcription activator that can interact with p50-NF-kappa B.
    Mol Cell Biol. 1992 Feb;12(2):674-84 PMID: 1732739
  23. Inhibition of NF-kappaB/Rel induces apoptosis of murine B cells.
    EMBO J. 1996 Sep 2;15(17):4682-90 PMID: 8887559
  24. Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells.
    J Virol. 1997 May;71(5):3563-73 PMID: 9094628
  25. p50-NF-kappaB complexes partially compensate for the absence of RelB: severely increased pathology in p50(-/-)relB(-/-) double-knockout mice.
    J Exp Med. 1997 Apr 7;185(7):1359-70 PMID: 9104822
  26. A-myb is expressed in bovine vascular smooth muscle cells during the late G1-to-S phase transition and cooperates with c-myc to mediate progression to S phase.
    Mol Cell Biol. 1997 May;17(5):2448-57 PMID: 9111313
  27. Induction of the transcription factor Sp1 during human cytomegalovirus infection mediates upregulation of the p65 and p105/p50 NF-kappaB promoters.
    J Virol. 1997 Jun;71(6):4638-48 PMID: 9151857
  28. Rel/NF-kappa B transcription factors and the control of apoptosis.
    Semin Cancer Biol. 1997 Apr;8(2):113-9 PMID: 9299589
  29. Inhibition of NF-kappa B activity induces apoptosis in murine hepatocytes.
    Am J Pathol. 1997 Oct;151(4):891-6 PMID: 9327720
  30. Nuclear factor-kappaB/Rel blocks transforming growth factor beta1-induced apoptosis of murine hepatocyte cell lines.
    Cell Growth Differ. 1997 Oct;8(10):1049-59 PMID: 9342183
  31. cAMP-induced NF-kappaB (p50/relB) binding to a c-myb intronic enhancer correlates with c-myb up-regulation and inhibition of erythroleukemia cell differentiation.
    Oncogene. 1997 Oct 9;15(15):1859-70 PMID: 9362453
  32. Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer.
    J Clin Invest. 1997 Dec 15;100(12):2952-60 PMID: 9399940
  33. NF-kappa B/Rel family members regulating the ICAM-1 promoter in monocytic THP-1 cells.
    Immunobiology. 1997 Dec;198(1-3):50-64 PMID: 9442377
  34. Physical interaction of the bHLH LYL1 protein and NF-kappaB1 p105.
    Oncogene. 1999 Jan 28;18(4):995-1005 PMID: 10023675
  35. Retinoids inhibit interleukin-12 production in macrophages through physical associations of retinoid X receptor and NFkappaB.
    J Biol Chem. 1999 Mar 19;274(12):7674-80 PMID: 10075655
  36. Inhibition of Ets-1 DNA binding and ternary complex formation between Ets-1, NF-kappaB, and DNA by a designed DNA-binding ligand.
    J Biol Chem. 1999 Apr 30;274(18):12765-73 PMID: 10212261
  37. Adenovirus-mediated expression of a ribozyme to c-myb mRNA inhibits smooth muscle cell proliferation and neointima formation in vivo.
    J Virol. 1999 Sep;73(9):7745-51 PMID: 10438864
  38. Tissue-selective expression of dominant-negative proteins for the regulation of vascular smooth muscle cell proliferation.
    Gene Ther. 1999 Jun;6(6):1184-91 PMID: 10455424
  39. Antisense strategies to inhibit restenosis.
    Antisense Nucleic Acid Drug Dev. 1999 Oct;9(5):487-92 PMID: 10555157
  40. The human cytomegalovirus chemokine receptor US28 mediates vascular smooth muscle cell migration.
    Cell. 1999 Nov 24;99(5):511-20 PMID: 10589679
  41. Control of apoptosis by Rel/NF-kappaB transcription factors.
    Oncogene. 1999 Nov 22;18(49):6910-24 PMID: 10602466
  42. Aberrant rel/nfkb genes and activity in human cancer.
    Oncogene. 1999 Nov 22;18(49):6938-47 PMID: 10602468
  43. Transcriptional elongation of c-myb is regulated by NF-kappaB (p50/RelB).
    Oncogene. 1999 Dec 2;18(51):7360-9 PMID: 10602492
  44. The Rel/NF-kappaB family directly activates expression of the apoptosis inhibitor Bcl-x(L).
    Mol Cell Biol. 2000 Apr;20(8):2687-95 PMID: 10733571
  45. Identification and characterization of nuclear factor kappaB binding sites in the murine bcl-x promoter.
    J Neurochem. 2000 Oct;75(4):1377-89 PMID: 10987817
  46. Attenuation of apoptosis underlies B lymphocyte stimulator enhancement of humoral immune response.
    J Exp Med. 2000 Oct 2;192(7):953-64 PMID: 11015437
  47. The RelA NF-kappaB subunit and the aryl hydrocarbon receptor (AhR) cooperate to transactivate the c-myc promoter in mammary cells.
    Oncogene. 2000 Nov 16;19(48):5498-506 PMID: 11114727
  48. Human T-cell lymphotropic virus type 1 Tax represses c-Myb-dependent transcription through activation of the NF-kappaB pathway and modulation of coactivator usage.
    Mol Cell Biol. 2001 Nov;21(21):7391-402 PMID: 11585920
  49. Localization of c-Myb and induction of apoptosis by antisense oligonucleotide c-Myb after angioplasty of porcine coronary arteries.
    Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1727-32 PMID: 11701457
  50. Distinct mechanisms for regulation of the interleukin-8 gene involve synergism and cooperativity between C/EBP and NF-kappa B.
    Mol Cell Biol. 1993 Nov;13(11):7191-8 PMID: 8413306
  51. Distinct NF-kappa B/Rel transcription factors are responsible for tissue-specific and inducible gene activation.
    Nature. 1993 Oct 21;365(6448):767-70 PMID: 7692309
  52. Expression of relB transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells.
    Development. 1993 Aug;118(4):1221-31 PMID: 8269849
  53. Differential regulation of the c-myc oncogene promoter by the NF-kappa B rel family of transcription factors.
    Mol Cell Biol. 1994 Feb;14(2):1039-44 PMID: 8289784
  54. Human cytomegalovirus late protein encoded by ie2: a trans-activator as well as a repressor of gene expression.
    J Gen Virol. 1994 Sep;75 ( Pt 9):2337-48 PMID: 8077932
  55. Differential interactions of Rel-NF-kappa B complexes with I kappa B alpha determine pools of constitutive and inducible NF-kappa B activity.
    EMBO J. 1994 Oct 3;13(19):4608-16 PMID: 7925301
  56. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family.
    Cell. 1995 Jan 27;80(2):331-40 PMID: 7834753
  57. Role of Rel-related factors in control of c-myc gene transcription in receptor-mediated apoptosis of the murine B cell WEHI 231 line.
    J Exp Med. 1995 Mar 1;181(3):1169-77 PMID: 7869034
  58. Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation.
    Science. 1995 Mar 10;267(5203):1485-8 PMID: 7878466
  59. Absolute dependence on kappa B responsive elements for initiation and Tat-mediated amplification of HIV transcription in blood CD4 T lymphocytes.
    EMBO J. 1995 Apr 3;14(7):1552-60 PMID: 7729429
  60. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B.
    Nature. 1995 Jul 13;376(6536):167-70 PMID: 7603567
  61. Human cytomegalovirus upregulates NF-kappa B activity by transactivating the NF-kappa B p105/p50 and p65 promoters.
    J Virol. 1995 Sep;69(9):5391-400 PMID: 7636984
  62. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation.
    Genes Dev. 1995 Nov 15;9(22):2723-35 PMID: 7590248
  63. Negative interaction between the RelA(p65) subunit of NF-kappaB and the progesterone receptor.
    J Biol Chem. 1996 Mar 15;271(11):6217-24 PMID: 8626413
  64. Inhibition of vascular smooth muscle cell proliferation by ribozymes that cleave c-myb mRNA.
    RNA. 1996 May;2(5):419-28 PMID: 8665409
  65. Maintenance of nuclear factor-kappa B/Rel and c-myc expression during CD40 ligand rescue of WEHI 231 early B cells from receptor-mediated apoptosis through modulation of I kappa B proteins.
    J Immunol. 1996 Jul 1;157(1):81-6 PMID: 8683159
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.76.11.5737-5747.2002
Published
2002-06-00
Pages
5737-47
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC137022
Subset
IM
Grants
NHLBI NIH HHS · P01 HL013262 · United States
NCI NIH HHS · R01 CA036355 · United States
NCI NIH HHS · CA36355 · United States
NHLBI NIH HHS · HL13262 · United States
External Links
PubMed source DOI: 10.1128/jvi.76.11.5737-5747.2002 PMC Full Text View journal details
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