This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hoberg, J. E.
Right arrow Articles by Mayo, M. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hoberg, J. E.
Right arrow Articles by Mayo, M. W.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2006, p. 457-471, Vol. 26, No. 2
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.2.457-471.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

I{kappa}B Kinase {alpha}-Mediated Derepression of SMRT Potentiates Acetylation of RelA/p65 by p300

Jamie E. Hoberg,1 Anita E. Popko,1,2 Catherine S. Ramsey,1 and Marty W. Mayo1*

Department of Biochemistry and Molecular Genetics, The University of Virginia, Charlottesville, Virginia 22908,1 Institute of Technical Biochemistry, Technical University of Lodz, 90-924 Lodz, Poland2

Received 15 September 2005/ Accepted 8 October 2005

Over the last several years, significant progress has been made in identifying chromatin-regulated events that govern NF-{kappa}B transcription. Using either laminin attachment or tumor necrosis factor alpha as a physiological stimulus of NF-{kappa}B activation, we demonstrate that I{kappa}B kinase {alpha} (IKK{alpha}) is recruited to chromatin in distinct phases. In the initial phase, IKK{alpha} is responsible for derepressing the silencing mediator for retinoic acid and thyroid hormone receptor (SMRT)-histone deacetylase 3 (HDAC3) corepressor complex from the p50 homodimer. However, in the latter phase, chromatin-bound IKK{alpha} coordinates the simultaneous phosphorylation of RelA/p65(S536) and SMRT(S2410) as detected by chromatin immunoprecipitation (ChIP) assays. Although phosphorylated SMRT remains bound to the active p50-RelA/p65 heterodimer of NF-{kappa}B, derepression of SMRT is evidenced by the loss of chromatin-associated HDAC3 activity. ChIP and re-ChIP analysis demonstrates that phosphorylation of RelA/p65(S536) and SMRT(S2410) occurs prior to acetylation of RelA/p65 at K310. Moreover, IKK{alpha}-induced phosphorylation of RelA/p65(S536) displaces corepressor activity, allowing p300-mediated acetylation of RelA/p65. Introduction of nonphosphorylatable mutants of RelA/p65 and SMRT proteins or the inhibition of IKK activity results in active repression of NF-{kappa}B promoters by tethering the SMRT-HDAC3 complex. Similar to phosphorylation within the Rel homology domain of RelA/p65, which governs an exchange of HDAC1 for CBP/p300 acetyltransferases, we demonstrate that phosphorylation within the transactivation domain of RelA/p65(S536) displaces SMRT-HDAC3 repressor activity, allowing p300 to acetylate RelA/p65.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Genetics, Box 800733, University of Virginia, Charlottesville, VA 22908. Phone: (434) 924-2509. Fax: (434) 982-1026. E-mail: mwm3y{at}virginia.edu.

Molecular and Cellular Biology, January 2006, p. 457-471, Vol. 26, No. 2
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.2.457-471.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Solt, L. A., Madge, L. A., May, M. J. (2009). NEMO-binding Domains of Both IKK{alpha} and IKK{beta} Regulate I{kappa}B Kinase Complex Assembly and Classical NF-{kappa}B Activation. J. Biol. Chem. 284: 27596-27608 [Abstract] [Full Text]  
  • Huang, B., Yang, X.-D., Zhou, M.-M., Ozato, K., Chen, L.-F. (2009). Brd4 Coactivates Transcriptional Activation of NF-{kappa}B via Specific Binding to Acetylated RelA. Mol. Cell. Biol. 29: 1375-1387 [Abstract] [Full Text]  
  • Tai, D. J. C., Su, C.-C., Ma, Y.-L., Lee, E. H. Y. (2009). SGK1 Phosphorylation of I{kappa}B Kinase {alpha} and p300 Up-regulates NF-{kappa}B Activity and Increases N-Methyl-D-aspartate Receptor NR2A and NR2B Expression. J. Biol. Chem. 284: 4073-4089 [Abstract] [Full Text]  
  • Van Gammeren, D., Damrauer, J. S., Jackman, R. W., Kandarian, S. C. (2009). The I{kappa}B kinases IKK{alpha} and IKK{beta} are necessary and sufficient for skeletal muscle atrophy. FASEB J. 23: 362-370 [Abstract] [Full Text]  
  • Lindstrom, T. M., Mohan, A. R., Johnson, M. R., Bennett, P. R. (2008). Histone Deacetylase Inhibitors Exert Time-Dependent Effects on Nuclear Factor-{kappa}B but Consistently Suppress the Expression of Proinflammatory Genes in Human Myometrial Cells. Mol. Pharmacol. 74: 109-121 [Abstract] [Full Text]  
  • Gao, N., Asamitsu, K., Hibi, Y., Ueno, T., Okamoto, T. (2008). AKIP1 Enhances NF-{kappa}B-dependent Gene Expression by Promoting the Nuclear Retention and Phosphorylation of p65. J. Biol. Chem. 283: 7834-7843 [Abstract] [Full Text]  
  • Yamaguchi, T., Kimura, J., Miki, Y., Yoshida, K. (2007). The Deubiquitinating Enzyme USP11 Controls an I{kappa}B Kinase {alpha} (IKK{alpha})-p53 Signaling Pathway in Response to Tumor Necrosis Factor {alpha} (TNF{alpha}). J. Biol. Chem. 282: 33943-33948 [Abstract] [Full Text]  
  • Wu, S., Flint, J. K., Rezvani, G., De Luca, F. (2007). Nuclear Factor-{kappa}B p65 Facilitates Longitudinal Bone Growth by Inducing Growth Plate Chondrocyte Proliferation and Differentiation and by Preventing Apoptosis. J. Biol. Chem. 282: 33698-33706 [Abstract] [Full Text]  
  • Saha, R. N., Jana, M., Pahan, K. (2007). MAPK p38 Regulates Transcriptional Activity of NF-{kappa}B in Primary Human Astrocytes via Acetylation of p65. J. Immunol. 179: 7101-7109 [Abstract] [Full Text]  
  • Neumann, M., Naumann, M. (2007). Beyond I{kappa}Bs: alternative regulation of NF-{kappa}B activity. FASEB J. 21: 2642-2654 [Abstract] [Full Text]  
  • Horion, J., Gloire, G., El Mjiyad, N., Quivy, V., Vermeulen, L., Vanden Berghe, W., Haegeman, G., Van Lint, C., Piette, J., Habraken, Y. (2007). Histone Deacetylase Inhibitor Trichostatin A Sustains Sodium Pervanadate-induced NF-{kappa}B Activation by Delaying I{kappa}B{alpha} mRNA Resynthesis: COMPARISON WITH TUMOR NECROSIS FACTOR {alpha}. J. Biol. Chem. 282: 15383-15393 [Abstract] [Full Text]  
  • Hansberger, M. W., Campbell, J. A., Danthi, P., Arrate, P., Pennington, K. N., Marcu, K. B., Ballard, D. W., Dermody, T. S. (2007). I{kappa}B Kinase Subunits {alpha} and {gamma} Are Required for Activation of NF-{kappa}B and Induction of Apoptosis by Mammalian Reovirus. J. Virol. 81: 1360-1371 [Abstract] [Full Text]  
  • Keslacy, S., Tliba, O., Baidouri, H., Amrani, Y. (2007). Inhibition of Tumor Necrosis Factor-{alpha}-Inducible Inflammatory Genes by Interferon-{gamma} Is Associated with Altered Nuclear Factor-{kappa}B Transactivation and Enhanced Histone Deacetylase Activity. Mol. Pharmacol. 71: 609-618 [Abstract] [Full Text]  
  • Fernandez-Majada, V., Aguilera, C., Villanueva, A., Vilardell, F., Robert-Moreno, A., Aytes, A., Real, F. X., Capella, G., Mayo, M. W., Espinosa, L., Bigas, A. (2007). Nuclear IKK activity leads to dysregulated Notch-dependent gene expression in colorectal cancer. Proc. Natl. Acad. Sci. USA 104: 276-281 [Abstract] [Full Text]  
  • Liu, Y., Smith, P. W., Jones, D. R. (2006). Breast Cancer Metastasis Suppressor 1 Functions as a Corepressor by Enhancing Histone Deacetylase 1-Mediated Deacetylation of RelA/p65 and Promoting Apoptosis. Mol. Cell. Biol. 26: 8683-8696 [Abstract] [Full Text]  
  • Liu, Y., Denlinger, C. E., Rundall, B. K., Smith, P. W., Jones, D. R. (2006). Suberoylanilide Hydroxamic Acid Induces Akt-mediated Phosphorylation of p300, Which Promotes Acetylation and Transcriptional Activation of RelA/p65. J. Biol. Chem. 281: 31359-31368 [Abstract] [Full Text]  
  • Sammons, M., Wan, S. S., Vogel, N. L., Mientjes, E. J., Grosveld, G., Ashburner, B. P. (2006). Negative Regulation of the RelA/p65 Transactivation Function by the Product of the DEK Proto-oncogene. J. Biol. Chem. 281: 26802-26812 [Abstract] [Full Text]  
  • Rosenfeld, M. G., Lunyak, V. V., Glass, C. K. (2006). Sensors and signals: a coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response. Genes Dev. 20: 1405-1428 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»