The 65-kDa Subunit of Human NF-kappa B Functions As a Potent Transcriptional Activator and a Target for V-Rel-mediated Repression

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1992 Mar 1

PMID 1542686

Citations 114

Authors

D W Ballard

E P Dixon

N J Peffer

H Bogerd

S Doerre

B Stein

W C Greene

Affiliations

Soon will be listed here.

Abstract

Molecular cloning of the polypeptide component of the Rel-related human p75 nucleoprotein complex has revealed its identity with the 65-kDa (p65) subunit of NF-kappa B. Functional analyses of chimeric proteins composed of NF-kappa B p65 C-terminal sequences linked to the DNA-binding domain of the yeast GAL4 polypeptide have indicated that the final 101 amino acids of NF-kappa B p65 comprise a potent transcriptional activation domain. Transient transfection of human T cells with an expression vector encoding NF-kappa B p65, but not NF-kappa B p50, produced marked transcriptional activation of a basal promoter containing duplicated kappa B enhancer motifs from the long terminal repeat of type 1 human immunodeficiency virus. These stimulatory effects of NF-kappa B p65 were synergistically enhanced by coexpression of NF-kappa B p50 but were completely inhibited by coexpression of the v-rel oncogene product. Together, these functional studies demonstrate that NF-kappa B p65 is a transactivating subunit of the heterodimeric NF-kappa B complex and serves as one cellular target for v-Rel-mediated transcriptional repression.

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References

Lowenthal J, Ballard D, Bogerd H, Bohnlein E, Greene W . Tumor necrosis factor-alpha activation of the IL-2 receptor-alpha gene involves the induction of kappa B-specific DNA binding proteins. J Immunol. 1989; 142(9):3121-8. View

Brownell E, Mittereder N, Rice N . A human rel proto-oncogene cDNA containing an Alu fragment as a potential coding exon. Oncogene. 1989; 4(7):935-42. View

Ullrich A, Berman C, Dull T, Gray A, Lee J . Isolation of the human insulin-like growth factor I gene using a single synthetic DNA probe. EMBO J. 1984; 3(2):361-4. PMC: 557350. DOI: 10.1002/j.1460-2075.1984.tb01812.x. View

Ruben S, Poteat H, Tan T, Kawakami K, Roeder R, Haseltine W . Cellular transcription factors and regulation of IL-2 receptor gene expression by HTLV-I tax gene product. Science. 1988; 241(4861):89-92. DOI: 10.1126/science.2838905. View

Ballard D, Bohnlein E, Lowenthal J, Wano Y, Franza B, Greene W . HTLV-I tax induces cellular proteins that activate the kappa B element in the IL-2 receptor alpha gene. Science. 1988; 241(4873):1652-5. DOI: 10.1126/science.241.4873.1652. View

Ma J, Ptashne M . Deletion analysis of GAL4 defines two transcriptional activating segments. Cell. 1987; 48(5):847-53. DOI: 10.1016/0092-8674(87)90081-x. View

Holbrook N, Gulino A, Ruscetti F . Cis-acting transcriptional regulatory sequences in the gibbon ape leukemia virus (GALV) long terminal repeat. Virology. 1987; 157(1):211-9. DOI: 10.1016/0042-6822(87)90330-8. View

Sadowski I, Ma J, Triezenberg S, Ptashne M . GAL4-VP16 is an unusually potent transcriptional activator. Nature. 1988; 335(6190):563-4. DOI: 10.1038/335563a0. View

Sen R, Baltimore D . Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986; 47(6):921-8. DOI: 10.1016/0092-8674(86)90807-x. View

10.

Baeuerle P, Baltimore D . I kappa B: a specific inhibitor of the NF-kappa B transcription factor. Science. 1988; 242(4878):540-6. DOI: 10.1126/science.3140380. View

11.

Kozak M . At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells. J Mol Biol. 1987; 196(4):947-50. DOI: 10.1016/0022-2836(87)90418-9. View

12.

Brent R, Ptashne M . A eukaryotic transcriptional activator bearing the DNA specificity of a prokaryotic repressor. Cell. 1985; 43(3 Pt 2):729-36. DOI: 10.1016/0092-8674(85)90246-6. View

13.

Wilhelmsen K, Eggleton K, Temin H . Nucleic acid sequences of the oncogene v-rel in reticuloendotheliosis virus strain T and its cellular homolog, the proto-oncogene c-rel. J Virol. 1984; 52(1):172-82. PMC: 254503. DOI: 10.1128/JVI.52.1.172-182.1984. View

14.

SANGER F, Nicklen S, Coulson A . DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977; 74(12):5463-7. PMC: 431765. DOI: 10.1073/pnas.74.12.5463. View

15.

Nolan G, Ghosh S, Liou H, Tempst P, Baltimore D . DNA binding and I kappa B inhibition of the cloned p65 subunit of NF-kappa B, a rel-related polypeptide. Cell. 1991; 64(5):961-9. DOI: 10.1016/0092-8674(91)90320-x. View

16.

Inoue J, Kerr L, Ransone L, Bengal E, Hunter T, Verma I . c-rel activates but v-rel suppresses transcription from kappa B sites. Proc Natl Acad Sci U S A. 1991; 88(9):3715-9. PMC: 51523. DOI: 10.1073/pnas.88.9.3715. View

17.

Urban M, Baeuerle P . The 65-kD subunit of NF-kappa B is a receptor for I kappa B and a modulator of DNA-binding specificity. Genes Dev. 1990; 4(11):1975-84. DOI: 10.1101/gad.4.11.1975. View

18.

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

19.

Gilmore T . NF-kappa B, KBF1, dorsal, and related matters. Cell. 1990; 62(5):841-3. DOI: 10.1016/0092-8674(90)90257-f. View

20.

Molitor J, WALKER W, Doerre S, Ballard D, Greene W . NF-kappa B: a family of inducible and differentially expressed enhancer-binding proteins in human T cells. Proc Natl Acad Sci U S A. 1990; 87(24):10028-32. PMC: 55308. DOI: 10.1073/pnas.87.24.10028. View