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

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2002 May 7

PMID 11992002

Citations 25

Authors

H Y Jiang

Constantinos Petrovas

Gail E Sonenshein

Affiliations

Soon will be listed here.

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.

Citing Articles

Atypical IκB Bcl3 enhances the generation of the NF-κB p52 homodimer.

Pan W, Deng L, Wang H, Wang V Front Cell Dev Biol. 2022; 10:930619.

PMID: 35990614 PMC: 9389042. DOI: 10.3389/fcell.2022.930619.

PPE38-Secretion-Dependent Proteins of Alter NF-kB Signalling and Inflammatory Responses in Macrophages.

Gallant J, Heunis T, Beltran C, Schildermans K, Bruijns S, Mertens I Front Immunol. 2021; 12:702359.

PMID: 34276695 PMC: 8284050. DOI: 10.3389/fimmu.2021.702359.

NF-κB/Rel Transcription Factors in Pancreatic Cancer: Focusing on RelA, c-Rel, and RelB.

Kabacaoglu D, Ruess D, Ai J, Algul H Cancers (Basel). 2019; 11(7).

PMID: 31277415 PMC: 6679104. DOI: 10.3390/cancers11070937.

The IκB Kinases Restrict Human Cytomegalovirus Infection.

Goodwin C, Munger J J Virol. 2019; 93(9).

PMID: 30760575 PMC: 6475784. DOI: 10.1128/JVI.02030-18.

Noncanonical NF-κB in Cancer.

Tegowski M, Baldwin A Biomedicines. 2018; 6(2).

PMID: 29874793 PMC: 6027307. DOI: 10.3390/biomedicines6020066.

References

Arsura M, Wu M, Sonenshein G . TGF beta 1 inhibits NF-kappa B/Rel activity inducing apoptosis of B cells: transcriptional activation of I kappa B alpha. Immunity. 1996; 5(1):31-40. DOI: 10.1016/s1074-7613(00)80307-6. View

Beldekas J, Gerstenfeld L, Sonenshein G, Franzblau C . Cell density and estradiol modulation of procollagen type III in cultured calf smooth muscle cells. J Biol Chem. 1982; 257(20):12252-6. View

Everett R, Dunlop M . Trans activation of plasmid-borne promoters by adenovirus and several herpes group viruses. Nucleic Acids Res. 1984; 12(15):5969-78. PMC: 320050. DOI: 10.1093/nar/12.15.5969. View

Everett R . Trans activation of transcription by herpes virus products: requirement for two HSV-1 immediate-early polypeptides for maximum activity. EMBO J. 1984; 3(13):3135-41. PMC: 557829. DOI: 10.1002/j.1460-2075.1984.tb02270.x. View

Cherrington J, Mocarski E . Human cytomegalovirus ie1 transactivates the alpha promoter-enhancer via an 18-base-pair repeat element. J Virol. 1989; 63(3):1435-40. PMC: 247847. DOI: 10.1128/JVI.63.3.1435-1440.1989. View

Reilly C, Kindy M, Brown K, Rosenberg R, Sonenshein G . Heparin prevents vascular smooth muscle cell progression through the G1 phase of the cell cycle. J Biol Chem. 1989; 264(12):6990-5. View

Sambucetti L, Cherrington J, Wilkinson G, Mocarski E . NF-kappa B activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. EMBO J. 1989; 8(13):4251-8. PMC: 401626. DOI: 10.1002/j.1460-2075.1989.tb08610.x. View

Duyao M, Buckler A, Sonenshein G . 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; 87(12):4727-31. PMC: 54190. DOI: 10.1073/pnas.87.12.4727. View

Brown K, Kindy M, Sonenshein G . Expression of the c-myb proto-oncogene in bovine vascular smooth muscle cells. J Biol Chem. 1992; 267(7):4625-30. View

10.

Blank V, Kourilsky P, Israel A . NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats. Trends Biochem Sci. 1992; 17(4):135-40. DOI: 10.1016/0968-0004(92)90321-y. View

11.

Mocarski E, Bonyhadi M, Salimi S, McCune J, KANESHIMA H . Human cytomegalovirus in a SCID-hu mouse: thymic epithelial cells are prominent targets of viral replication. Proc Natl Acad Sci U S A. 1993; 90(1):104-8. PMC: 45608. DOI: 10.1073/pnas.90.1.104. View

12.

Doerre S, Sista P, Sun S, Ballard D, Greene W . 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; 90(3):1023-7. PMC: 45803. DOI: 10.1073/pnas.90.3.1023. View

13.

Grilli M, Chiu J, Lenardo M . NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. Int Rev Cytol. 1993; 143:1-62. DOI: 10.1016/s0074-7696(08)61873-2. View

14.

Grimm S, Baeuerle P . The inducible transcription factor NF-kappa B: structure-function relationship of its protein subunits. Biochem J. 1993; 290 ( Pt 2):297-308. PMC: 1132272. DOI: 10.1042/bj2900297. View

15.

Lemstrom K, Bruning J, Bruggeman C, Lautenschlager I, Hayry P . Cytomegalovirus infection enhances smooth muscle cell proliferation and intimal thickening of rat aortic allografts. J Clin Invest. 1993; 92(2):549-58. PMC: 294886. DOI: 10.1172/JCI116622. View

16.

Raj G, Safak M, MacDonald G, Khalili K . 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; 70(9):5944-53. PMC: 190614. DOI: 10.1128/JVI.70.9.5944-5953.1996. View

17.

Kieran M, Blank V, Logeat F, Vandekerckhove J, Lottspeich F, Le Bail O . The DNA binding subunit of NF-kappa B is identical to factor KBF1 and homologous to the rel oncogene product. Cell. 1990; 62(5):1007-18. DOI: 10.1016/0092-8674(90)90275-j. View

18.

Ghosh S, Gifford A, Riviere L, Tempst P, Nolan G, Baltimore D . Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal. Cell. 1990; 62(5):1019-29. DOI: 10.1016/0092-8674(90)90276-k. View

19.

Ruben S, Dillon P, Schreck R, Henkel T, Chen C, Maher M . Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. Science. 1991; 251(5000):1490-3. DOI: 10.1126/science.2006423. View

20.

Baeuerle P . The inducible transcription activator NF-kappa B: regulation by distinct protein subunits. Biochim Biophys Acta. 1991; 1072(1):63-80. DOI: 10.1016/0304-419x(91)90007-8. View