Potentiation of tumor necrosis factor-induced NF-kappa B activation by deacetylase inhibitors is associated with a delayed cytoplasmic reappearance of I kappa B alpha
[en] Previous studies have implicated acetylases and deacetylases in regulating the transcriptional activity of NF-kappaB. Here, we show that inhibitors of deacetylases such as trichostatin A (TSA) and sodium butyrate (NaBut) potentiated TNF-induced expression of several natural NF-kappaB-driven promoters. This transcriptional synergism observed between TNF and TSA (or NaBut) required intact kappaB sites in all promoters tested and was biologically relevant as demonstrated by RNase protection on two instances of endogenous NF-kappaB-regulated gene transcription. Importantly, TSA prolonged both TNF-induced DNA-binding activity and the presence of NF-kappaKB in the nucleus. We showed that the p65 subunit of NF-kappaB was acetylated in vivo. However, this acetylation was weak, suggesting that other mechanisms could be implicated in the potentiated binding and transactivation activities of NF-kappaB after TNF plus TSA versus TNF treatment. Western blot and immunofluorescence confocal microscopy experiments revealed a delay in the cytoplasmic reappearance of the IkappaBalpha inhibitor that correlated temporally with the prolonged intranuclear binding and presence of NF-kappaB. This delay was due neither to a defect in IkappaBalpha mRNA production nor to a nuclear retention of IkappaBalpha but was rather due to a persistent proteasome-mediated degradation of IkappaBalpha. A prolongation of IkappaB kinase activity could explain, at least partially, the delayed IkappaBalpha cytoplasmic reappearance observed in presence of TNF plus TSA.
Research Center/Unit :
Giga-Signal Transduction - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Adam, Emmanuelle
Quivy, Vincent
Bex, Françoise
Chariot, Alain ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Collette, Yves
Vanhulle, Caroline
Haterte, Stéphanie ; Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique
Goffin, Véronique ; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie
Potentiation of tumor necrosis factor-induced NF-kappa B activation by deacetylase inhibitors is associated with a delayed cytoplasmic reappearance of I kappa B alpha
Publication date :
September 2003
Journal title :
Molecular and Cellular Biology
ISSN :
0270-7306
eISSN :
1098-5549
Publisher :
Amer Soc Microbiology, Washington, United States - Washington
Volume :
23
Issue :
17
Pages :
6200-6209
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] Télévie [BE]
Aoudjit, F., N. Brochu, B. Belanger, C. Stratowa, J. Hiscott, and M. Audette. 1997. Heterodimeric retinoic acid receptor-β and retinoid X receptor-α complexes stimulate expression of the intercellular adhesion molecule-1 gene. Cell Growth Differ. 8:335-342.
Arenzana-Seisdedos, F., P. Turpin, M. Rodriguez, D. Thomas, R. T. Hay, J. L. Virelizier, and C. Dargemont. 1997. Nuclear localization of IκBα promotes active transport of NF-κB from the nucleus to the cytoplasm. J. Cell Sci. 110:369-378.
Ashburner, B. P., S. D. Westerheide, and A. S. Baldwin, Jr. 2001. The p65 (RelA) subunit of NF-KB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression. Mol. Cell. Biol. 21:7065-7077.
Baldwin, A. S., Jr. 2001. Series introduction: the transcription factor NF-κB and human disease. J. Clin. Investig. 107:3-6.
Ben Neriah, Y. 2002. Regulatory functions of ubiquitination in the immune system. Nat. Immunol. 3:20-26.
Bordonaro, M., J. M. Mariadason, F. Aslam, B. G. Heerdt, and L. H. Augenlicht. 1999. Butyrate-induced apoptotic cascade in colonic carcinoma cells: modulation of the β-catenin-Tcf pathway and concordance with effects of sulindac and trichostatin A but not curcumin. Cell Growth Differ. 10:713-720.
Boyes, J., P. Byfield, Y. Nakatani, and V. Ogryzko. 1998. Regulation of activity of the transcription factor GATA-1 by acetylation. Nature 396:594-598.
Bulteau, A., I. Petropoulos, and B. Friguet. 2000. Age-related alterations of proteasome structure and function in aging epidermis. Exp. Gerontol. 35:767-777.
Calomme, C., T.-L. Nguyen, Y. de Launoit, V. Kiermer, L. Droogmans, A. Burny, and C. Van Lint. 2002. Upstream stimulatory factors binding to an E box motif in the R region of the bovine leukemia virus long terminal repeat stimulates viral gene expression. J. Biol. Chem. 277:8775-8789.
Chen, H., M. Tini, and R. M. Evans. 2001. HATs on and beyond chromatin. Curr. Opin. Cell Biol. 13:218-224.
Chen, L., W. Fischle, E. Verdin, and W. C. Greene. 2001. Duration of nuclear NF-κB action regulated by reversible acetylation. Science 293:1653-1657.
Chen, L., Y. Mu, and W. C. Greene. 2002. Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-κB. EMBO J. 21:6539-6548.
Dai, R.-M., E. Chen, D. L. Longo, C. M. Gorbea, and C.-C. H. Li. 1998. Involvement of valosin-containing protein, an ATPase co-purified with IκBα and 26 S proteasome, in ubiquitin-proteasome-mediated degradation of IκBα. J. Biol. Chem. 273:3562-3573.
de Launoit, Y., M. Audette, H. Pelczar, S. Plaza, S., and J. L. Baert, 1998. The transcription of the intercellular adhesion molecule-1 is regulated by Ets transcription factors. Oncogene 16:2065-2073.
Duckett, C. S., N. D. Perkins, T. F. Kowalik, R. M. Schmid, E. S. Huang, A. S. Baldwin, Jr., and G. J. Nabel. 1993. Dimerization of NF-κB2 with RelA(p65) regulates DNA binding, transcriptional activation, and inhibition by an IκB (MAD-3). Mol. Cell. Biol. 13:1315-1322.
Eickhoff, B., L. Germeroth, C. Stahl, G. Köhler, S. Rüller, M. Schlaak, and J. van der Bosch. 2000. Trichostatin A-mediated regulation of gene expression and protein kinase activities: reprogramming tumor cells for ribotoxic stress-induced apoptosis. Biol. Chem. 381:1127-1132.
El Kharroubi, A., G. Piras, R. Zensen, and M. A. Martin. 1998. Transcriptional activation of the integrated chromatin-associated human immunodeficiency virus type 1 promoter. Mol. Cell. Biol. 18:2535-2544.
Gerritsen, M. E., A. J. Williams, A. S. Neish, S. Moore, Y. Shi, and T. Collins. 1997. CREB-binding protein/p300 are transcriptional coactivators of p65. Proc. Natl. Acad. Sci. USA 94:2927-2932.
Ghosh, S., and M. Karin, 2002. Missing pieces in the NF-κB puzzle. Cell 109:S82-S96.
Giuliano, M., M. Lauricelia, G. Calvaruso, M. Carabillo, S. Emanuele, R. Vento, and G. Tesoriere, 1999. The apoptotic effects and synergistic interaction of sodium butyrate and MG132 in human retinoblastoma Y79 cells. Cancer Res. 59:5586-5595.
Gu, W., and R. G. Roeder. 1997. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90:595-606.
Ichiyama, T., K. Okada, J. M. Lipton, T. Matsubara, T. Hayashi, and S. Furukawa. 2000. Sodium valproate inhibits production of TNF-α and IL-6 and activation of NF-κB. Brain Res. 857:246-251.
Israel, A. 2000. The IKK complex: an integrator of all signals that activate NF-kappaB? Trends Cell Biol. 10:129-133.
Ito, K., P. J. Barnes, and I. M. Adcock. 2000. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin 1β-induced histone H4 acetylation on lysines 8 and 12. Mol. Cell. Biol. 20:6891-6903.
Jaffray, E., K. M. Wood, and R. Hay, 1995. Domain organization of IκBα and sites of interaction with NF-κB p65. Mol. Cell. Biol. 15:2166-2172.
Karin, M., and Y. Ben Neriah. 2000. Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu. Rev. Immunol. 18:621-663.
Kiernan, R., V. Brès, R. W. M. Ng, M.-P. Coudart, S. El Messaoudi, C. Sardet, D.-Y. Jin, S. Emiliani, and M. Benkirane. 2003. Post-activation turn-off of NF-κB-dependent transcription is regulated by acetylation of p65. J. Biol. Chem. 278:2758-2766.
Lee, S. K., J. H. Kim, Y. C. Lee, J. Cheong, and J. W. Lee. 2000. Silencing mediator of retinoic acid and thyroid hormone receptors as a novel transcriptional corepressor molecule of activating protein 1, nuclear factor-κB, and serum response factor. J. Biol. Chem. 275:12470-12474.
Merika, M., A. J. Williams, G. Chen, T. Collins, and D. Thanos. 1998. Recruitment of CBP/p300 by the IFN-β enhanceosome is required for synergistic activation of transcription. Mol. Cell 1:277-287.
Munshi, N., M. Merika, J. Yie, K. Senger, G. Chen, and D. Thanos. 1998. Acetylation of HMG I(Y) by CBP turns off IFN-β expression by disrupting the enhanceosome. Mol. Cell 2:457-4467.
Na, S. Y., S. K. Lee, S. J. Han, H. S. Choi, S. Y. Im, and J. W. Lee. 1998. Steroid receptor coactivator-1 interacts with the p50 subunit and coactivates nuclear factor κB-mediated transactivations. J. Biol. Chem. 273:10831-10834.
Osborn, L., S. Kunkel, and G. J. Nabel. 1989. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor κ B. Proc. Natl. Acad. Sci. USA 86:2336-2340.
Ott, M., J. L. Lovett, L. Mueller, and E. Verdin. 1998. Superinduction of IL-8 in T cells by HIV-1 Tat protein is mediated through NF-κB factors. J. Immunol. 160:2872-2880.
Perkins, N. D., L. K. Felzien, J. C. Betts, K. Leung, D. H. Beach, and G. J. Nabel. 1997. Regulation of NF-κB by cyclin-dependent kinases associated with the p300 coactivator. Science 275:523-527.
Rodriguez, M. S., J. Thompson, R. T. Hay, and C. Dargemont. 1999. Nuclear retention of IκB protects it from signal-induced degradation and inhibits nuclear factor κB transcriptional activation. J. Biol. Chem. 274:9108-9115.
Saccani, S., S. Pantano, and G. Natoli. 2001. Two waves of nuclear factor κB recruitment to target promoters. J. Exp. Med. 193:1351-1359.
Saccani, S., S. Pantano, and G. Natoli. 2002. p38-dependent marking of inflammatory genes for increased NF-κB recruitment. Nat. Immunol. 3:69-75.
Sakurai, H., H. Chiba, H. Miyoshi, T. Sugita, and W. Toriumi. 1999. IκB kinase phosphorylates NF-κB p65 subunit on serine 536 in the transactivation domain J. Biol. Chem. 274:30353-30356.
Schoonbroodt, S., V. Ferreira, M. Best-Belpomme, J. R. Boelaert, S. Legrand-Poels, M. Korner, and J. Piette. 2000. Crucial role of the amino-terminal tyrosine residue 42 and the carboxyl-terminal PEST domain of IκB alpha in NF-κB activation by an oxidative stress. J. Immunol. 164:4292-4300.
Seigneurin-Berny, D., A. Verdel, S. Curtet, C. Lemercier, J. Garin, S. Rousseaux, and S. Khochbin, 2001. Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways. Mol. Cell. Biol. 21:8035-8044.
Sheppard, K. A., D. W. Rose, Z. K. Haque, R. Kurokawa, E. McInerney, S. Westin, D. Thanos, M. G. Rosenfeld, C. K. Glass, and T. Collins, 1999. Transcriptional activation by NF-κB requires multiple coactivators. Mol. Cell. Biol. 19:6367-6378.
Spencer, T. E., G. Jenster, M. M. Burein, C. D. Allis, J. Zhou, C. A. Mizzen, N. J. McKenna, S. A. Onate, S. Y. Tsai, M. J. Tsai, and B. W. O'Malley. 1997. Steroid receptor coactivator 1 is a histone acetyltransferase. Nature 389:194-198.
Spiegelman, V. S., T. J. Slaga, M. Pagano, T. Minamoto, Z. Ronai, and S. Y. Fuchs. 2000. Wnt/β-catenin signaling induces the expression and activity of βTRCP ubiquitin ligase receptor. Mol. Cell 5:877-882.
Spiegelman, V. S., P. Stavropoulos, E. Latres, M. Pagano, Z. Ronai, T. J. Slaga, and S. Y. Fuchs. 2001. Induction of β-transducin repeat-containing protein by JNK signaling and its role in the activation of NF-κB. J. Biol. Chem. 276:27152-27158.
Turpin, P., R. H. Hay, and C. Dargemont. 1999. Characterization of IκBα nuclear import pathway. J. Biol. Chem. 274:6804-6812.
Vanden Berghe, W., K. De Bosscher, E. Boone, S. Plaisance, and G. Haegeman. 1999. The nuclear factor-κB engages CBP/p300 and histone acetyltransferase activity for transcriptional activation of the interleukin 6 gene promoter. J. Biol. Chem. 274:32091-32098.
Van Lint, C., S. Emiliani, M. Ott, and E. Verdin. 1996. Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation. EMBO J. 15:1112-1120.
Vermeulen, L., G. De Wilde, S. Notebaert, W. Vanden Berghe, and G. Haegeman. 2002. Regulation of the transcriptional activity of the nuclear factor-κB p65 subunit. Biochem. Pharmacol. 64:963-970.
West, M. J., A. D. Lowe, and J. Karn. 2001. Activation of human immuno-deficiency virus transcription in T cells revisited: NF-κB p65 stimulates transcriptional elongation. J. Virol. 75:8524-8537.
Yin, L., G. Laevsky, and C. Giardina. 2001. Butyrate suppression of colonocyte NF-κB activation and cellular proteasome activity. J. Biol. Chem. 276:44641-44646.
Zhong, H., H. SuYang, H. Erdjument-Bromage, P. Tempst, and S. Ghosh. 1997. The transcriptional activity of NF-κB is regulated by the IκB-associated PKAc subunit through a cyclic AMP-independent mechanism. Cell 89:413-424.
Zhong, H., R. E. Voll, and S. Ghosh. 1998. Phosphorylation of NF-κB p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Mol. Cell 1:661-671.
Zhong, H., M. J. May, E. Jimi, and S. Ghosh. 2002. The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1. Mol. Cell 9:625-636.
