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Science 10 March 1995:
Vol. 267. no. 5203, pp. 1485 - 1488
DOI: 10.1126/science.7878466

Articles

Science, Vol 267, Issue 5203, 1485-1488
Copyright © 1995 by American Association for the Advancement of Science


articles

Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation

K Brown, S Gerstberger, L Carlson, G Franzoso, and U Siebenlist

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1876.

I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal-induced phosphorylation or degradation, and NF-kappa B could not be activated. These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B.


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   Abstract »    Full Text »    PDF »
cAMP targeting of p38 MAP kinase inhibits thrombin-induced NF-{kappa}B activation and ICAM-1 expression in endothelial cells.
A. Rahman, K. N. Anwar, Mohd. Minhajuddin, K. M. Bijli, K. Javaid, A. L. True, and A. B. Malik (2004)
Am J Physiol Lung Cell Mol Physiol 287, L1017-L1024
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HERC5, a HECT E3 ubiquitin ligase tightly regulated in LPS activated endothelial cells.
R. Kroismayr, U. Baranyi, C. Stehlik, A. Dorfleutner, B. R. Binder, and J. Lipp (2004)
J. Cell Sci. 117, 4749-4756
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NF-{kappa}B and AP-1 Connection: Mechanism of NF-{kappa}B-Dependent Regulation of AP-1 Activity.
S. Fujioka, J. Niu, C. Schmidt, G. M. Sclabas, B. Peng, T. Uwagawa, Z. Li, D. B. Evans, J. L. Abbruzzese, and P. J. Chiao (2004)
Mol. Cell. Biol. 24, 7806-7819
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Myocyte hypertrophy and apoptosis: a balancing act.
V. P.M van Empel and L. J De Windt (2004)
Cardiovasc Res 63, 487-499
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Effects of the proteasome inhibitor PS-341 on tumor growth in HTLV-1 Tax transgenic mice and Tax tumor transplants.
S. Mitra-Kaushik, J. C. Harding, J. L. Hess, and L. Ratner (2004)
Blood 104, 802-809
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Transcriptional Mechanisms Regulating Alveolar Epithelial Cell-specific CCL5 Secretion in Pulmonary Tuberculosis.
M. I. Wickremasinghe, L. H. Thomas, C. M. O'Kane, J. Uddin, and J. S. Friedland (2004)
J. Biol. Chem. 279, 27199-27210
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NF-{kappa}B Activation by the Chemopreventive Dithiolethione Oltipraz Is Exerted through Stimulation of MEKK3 Signaling.
C. W. Nho and P. J. O'Dwyer (2004)
J. Biol. Chem. 279, 26019-26027
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p53 Induces NF-{kappa}B Activation by an I{kappa}B Kinase-independent Mechanism Involving Phosphorylation of p65 by Ribosomal S6 Kinase 1.
J. Bohuslav, L.-f. Chen, H. Kwon, Y. Mu, and W. C. Greene (2004)
J. Biol. Chem. 279, 26115-26125
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{beta}-Arrestin inhibits NF-{kappa}B activity by means of its interaction with the NF-{kappa}B inhibitor I{kappa}B{alpha}.
D. S. Witherow, T. R. Garrison, W. E. Miller, and R. J. Lefkowitz (2004)
PNAS 101, 8603-8607
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Activation of the NF-{kappa}B Pathway in Human Cytomegalovirus-Infected Cells Is Necessary for Efficient Transactivation of the Major Immediate-Early Promoter.
I. B. DeMeritt, L. E. Milford, and A. D. Yurochko (2004)
J. Virol. 78, 4498-4507
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Human T-cell Lymphotropic Virus Type 1 Tax Induction of Biologically Active NF-{kappa}B Requires I{kappa}B Kinase-1-mediated Phosphorylation of RelA/p65.
A. M. O'Mahony, M. Montano, K. Van Beneden, L.-F. Chen, and W. C. Greene (2004)
J. Biol. Chem. 279, 18137-18145
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