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PMID: 1588976 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Rapid induction in regenerating liver of RL/IF-1 (an I kappa B that inhibits NF-kappa B, RelB-p50, and c-Rel-p50) and PHF, a novel kappa B site-binding complex.

Molecular and cellular biology ·Vol. 12 ·No. 6 ·1992-06-00 ·Pages 2898-908

Tewari M, Dobrzanski P, Mohn KL, Cressman DE, Hsu JC, Bravo R, Taub R

Abstract

The liver is one of the few adult tissues that has the capacity to regenerate following hepatectomy or toxic damage. In examining the early growth response during hepatic regeneration, we found that a highly induced immediate-early gene in regenerating liver encodes RL/IF-1 (regenerating liver inhibitory factor) and is the rat homolog of human MAD-3 and probably of chicken pp40. RL/IF-1 has I kappa B activity of broad specificity in that it inhibits the binding of p50-p65 NF-kappa B, c-Rel-p50, and RelB-p50, but not p50 homodimeric NF-kappa B, to kappa B sites. Like RL/IF-1, several members of the NF-kappa B and rel family of transcription factors are immediate-early genes in regenerating liver and mitogen-treated cells. We examined changes in kappa B site binding activity during liver regeneration and discovered a rapidly induced novel kappa B site-binding complex designated PHF [posthepatectomy factor(s)]. PHF is induced over 1,000-fold within minutes posthepatectomy in a protein synthesis-independent manner, with peak activity at 30 min, and is not induced by sham operation. PHF is distinct from p50-p65 NF-kappa B, which is present only in the inactive form in liver posthepatectomy. Although early PHF complexes do not interact strongly with anti-p50 antibodies, PHF complexes present later (3 to 5 h) posthepatectomy react strongly, suggesting that they contain a p50 NF-kappa B subunit. Unlike p50-p65 NF-kappa B, c-Rel-p50, and RelB-p50 complexes, PHF binding to kappa B sites is not inhibited by RL/IF-1. One role of RL/IF-1 in liver regeneration may be to inhibit p50-p65 NF-kappa B activity present in hepatic cells, allowing for the preferential binding of PHF to kappa B sites. Because PHF is induced immediately posthepatectomy in the absence of de novo protein synthesis, PHF could have a role in the regulation of liver-specific immediate-early genes in regenerating liver.

MeSH Terms
Animals Base Sequence DNA-Binding Proteins/metabolism Female Gene Expression I-kappa B Proteins Liver Regeneration Macromolecular Substances Molecular Sequence Data NF-KappaB Inhibitor alpha NF-kappa B/antagonists & inhibitors,metabolism Nuclear Proteins/metabolism Oligodeoxyribonucleotides/chemistry Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-rel RNA, Messenger/genetics Rats Sequence Alignment Time Factors Transcription Factors/metabolism
Chemicals
DNA-Binding Proteins I-kappa B Proteins Macromolecular Substances NF-kappa B NFKBIA protein, human Nfkbia protein, rat Nuclear Proteins Oligodeoxyribonucleotides Proto-Oncogene Proteins Proto-Oncogene Proteins c-rel RNA, Messenger Transcription Factors NF-KappaB Inhibitor alpha
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Tewari M
Department of Human Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104-6145.
Dobrzanski P
Mohn K L
Cressman D E
Hsu J C
Bravo R
Taub R
References (52)
52 references, click to expand
  1. Immediate-early gene expression differs between regenerating liver, insulin-stimulated H-35 cells, and mitogen-stimulated Balb/c 3T3 cells. Liver-specific induction patterns of gene 33, phosphoenolpyruvate carboxykinase, and the jun, fos, and egr families.
    J Biol Chem. 1990 Dec 15;265(35):21914-21 PMID: 2123877
  2. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  3. 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
  4. Rel-associated pp40: an inhibitor of the rel family of transcription factors.
    Science. 1991 Sep 13;253(5025):1268-71 PMID: 1891714
  5. The rel-associated pp40 protein prevents DNA binding of Rel and NF-kappa B: relationship with I kappa B beta and regulation by phosphorylation.
    Genes Dev. 1991 Aug;5(8):1464-76 PMID: 1907941
  6. Cloning of a mitogen-inducible gene encoding a kappa B DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs.
    Nature. 1990 Nov 1;348(6296):76-80 PMID: 2234062
  7. 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
  8. The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF-kappa B function.
    Cell. 1990 Nov 16;63(4):803-14 PMID: 2225078
  9. 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
  10. NF-kappa B contacts DNA by a heterodimer of the p50 and p65 subunit.
    EMBO J. 1991 Jul;10(7):1817-25 PMID: 2050119
  11. Convergence of Ets- and notch-related structural motifs in a heteromeric DNA binding complex.
    Science. 1991 Aug 16;253(5021):762-8 PMID: 1876833
  12. Cloning of the DNA-binding subunit of human nuclear factor kappa B: the level of its mRNA is strongly regulated by phorbol ester or tumor necrosis factor alpha.
    Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):966-70 PMID: 1992489
  13. Angiotensinogen gene-inducible enhancer-binding protein 1, a member of a new family of large nuclear proteins that recognize nuclear factor kappa B-binding sites through a zinc finger motif.
    Mol Cell Biol. 1991 May;11(5):2887-95 PMID: 2017183
  14. Purified I kappa B-beta is inactivated upon dephosphorylation.
    J Biol Chem. 1992 Jan 5;267(1):239-46 PMID: 1309735
  15. Sequence of rat RL/IF-1 encoding an IkappaB, and comparison with related proteins containing notch-like repeats [corrected].
    Nucleic Acids Res. 1992 Feb 11;20(3):607 PMID: 1741294
  16. 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
  17. Induction of NF-kappa B DNA-binding activity during the G0-to-G1 transition in mouse fibroblasts.
    Mol Cell Biol. 1991 Oct;11(10):4943-51 PMID: 1922027
  18. The jun and fos protein families are both required for cell cycle progression in fibroblasts.
    Mol Cell Biol. 1991 Sep;11(9):4466-72 PMID: 1908553
  19. Primary response genes induced by growth factors and tumor promoters.
    Annu Rev Biochem. 1991;60:281-319 PMID: 1883198
  20. 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
  21. Identification of Ets- and notch-related subunits in GA binding protein.
    Science. 1991 Aug 16;253(5021):789-92 PMID: 1876836
  22. Processing of the precursor of NF-kappa B by the HIV-1 protease during acute infection.
    Nature. 1991 Apr 18;350(6319):625-6 PMID: 2017258
  23. Nuclear factor kappa B activates proenkephalin transcription in T lymphocytes.
    Mol Cell Biol. 1991 Feb;11(2):1017-22 PMID: 1990263
  24. The immediate-early growth response in regenerating liver and insulin-stimulated H-35 cells: comparison with serum-stimulated 3T3 cells and identification of 41 novel immediate-early genes.
    Mol Cell Biol. 1991 Jan;11(1):381-90 PMID: 1986233
  25. Maintenance of NF-kappa B activity is dependent on protein synthesis and the continuous presence of external stimuli.
    Mol Cell Biol. 1991 Jan;11(1):259-66 PMID: 1986224
  26. Vectors for selective expression of cloned DNAs by T7 RNA polymerase.
    Gene. 1987;56(1):125-35 PMID: 3315856
  27. Complexity of the early genetic response to growth factors in mouse fibroblasts.
    Mol Cell Biol. 1988 May;8(5):2140-8 PMID: 2898731
  28. A liver-specific DNA-binding protein recognizes multiple nucleotide sites in regulatory regions of transthyretin, alpha 1-antitrypsin, albumin, and simian virus 40 genes.
    Proc Natl Acad Sci U S A. 1988 Jun;85(11):3840-4 PMID: 2836860
  29. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor.
    Cell. 1988 Apr 22;53(2):211-7 PMID: 3129195
  30. I kappa B: a specific inhibitor of the NF-kappa B transcription factor.
    Science. 1988 Oct 28;242(4878):540-6 PMID: 3140380
  31. Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene, c-rel.
    Science. 1987 Oct 30;238(4827):692-4 PMID: 3118464
  32. Multiple nuclear factors interact with the immunoglobulin enhancer sequences.
    Cell. 1986 Aug 29;46(5):705-16 PMID: 3091258
  33. Complexity of the primary genetic response to mitogenic activation of human T cells.
    Mol Cell Biol. 1989 Mar;9(3):1041-8 PMID: 2498643
  34. 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
  35. NF-kappa B: a pleiotropic mediator of inducible and tissue-specific gene control.
    Cell. 1989 Jul 28;58(2):227-9 PMID: 2665943
  36. Regulation of liver growth: protooncogenes and transforming growth factors.
    Lab Invest. 1989 Jan;60(1):4-13 PMID: 2642989
  37. Transcriptional induction of the murine c-rel gene with serum and phorbol-12-myristate-13-acetate in fibroblasts.
    Mol Cell Biol. 1989 Nov;9(11):5239-43 PMID: 2601720
  38. Cloning of tetradecanoyl phorbol ester-induced 'primary response' sequences and their expression in density-arrested Swiss 3T3 cells and a TPA non-proliferative variant.
    Oncogene. 1987;1(3):263-70 PMID: 3330774
  39. 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 Oct;52(1):172-82 PMID: 6090694
  40. Insulin as a growth factor in rat hepatoma cells. Stimulation of proto-oncogene expression.
    J Biol Chem. 1987 Aug 5;262(22):10893-7 PMID: 3301843
  41. Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc.
    Proc Natl Acad Sci U S A. 1987 Mar;84(5):1182-6 PMID: 3469660
  42. Identification of a set of genes expressed during the G0/G1 transition of cultured mouse cells.
    EMBO J. 1985 Dec 1;4(12):3145-51 PMID: 3841511
  43. NF-kappa B, KBF1, dorsal, and related matters.
    Cell. 1990 Sep 7;62(5):841-3 PMID: 2203533
  44. 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
  45. Avian reticuloendotheliosis virus-transformed lymphoid cells contain multiple pp59v-rel complexes.
    J Virol. 1990 Feb;64(2):584-91 PMID: 2153225
  46. Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B.
    Nature. 1990 Apr 12;344(6267):678-82 PMID: 2157987
  47. The product of fem-1, a nematode sex-determining gene, contains a motif found in cell cycle control proteins and receptors for cell-cell interactions.
    Cell. 1990 Mar 23;60(6):981-90 PMID: 2317869
  48. Analysis of cDNA for human erythrocyte ankyrin indicates a repeated structure with homology to tissue-differentiation and cell-cycle control proteins.
    Nature. 1990 Mar 1;344(6261):36-42 PMID: 2137557
  49. Purified human I kappa B can rapidly dissociate the complex of the NF-kappa B transcription factor with its cognate DNA.
    Cell. 1990 Apr 20;61(2):255-65 PMID: 2184941
  50. Liver regeneration: molecular mechanisms of growth control.
    FASEB J. 1990 Feb 1;4(2):176-87 PMID: 2404819
  51. Molecular cloning of gene sequences regulated by platelet-derived growth factor.
    Cell. 1983 Jul;33(3):939-47 PMID: 6872001
  52. A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site.
    Mol Cell Biol. 1992 Feb;12(2):685-95 PMID: 1531086
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.6.2898-2908.1992
Published
1992-06-00
Pages
2898-908
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC364484
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.12.6.2898-2908.1992 PMC Full Text View journal details
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