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J. Biol. Chem., Vol. 279, Issue 6, 4017-4026, February 6, 2004
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Functionally Interacts with Histone Acetyltransferase Complexes*



¶
From the
Department of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, D-89081 Ulm, Germany and the
Department of Genetics and Microbiology, Charles University, 12844 Prague, Czech Republic
Interleukin-1
(IL-1
) is an inflammatory cytokine acting extracellularly via membrane receptors. Interestingly, a significant portion of synthesized IL-1
is not secreted; instead, it is actively translocated into the cell nucleus. IL-1
was indeed shown to be involved in certain intracellular processes, such as control of proliferation, apoptosis, or migration, however, the mechanisms of such actions are not known. Here we show that intracellular IL-1
fused to the Gal4p DNA-binding domain (Gal4BD) possesses strong transactivation potential that can be boosted by overexpression of the transcriptional coactivator p300. We demonstrate that the IL-1
precursor interacts via its N-terminal peptide (IL-1NTP) with histone acetyltransferases p300, PCAF, Gcn5 and with the adaptor component Ada3, and that it integrates into the PCAF·p300 complex in a non-destructive manner. In analogy with known acidic coactivators, yeast strains expressing Gal4BD/IL-1NTP display a toxic phenotype that can be relieved by depletion of various components of the SAGA complex. Our data provide the first solid evidence for the nuclear target of the IL-1
precursor and suggest its novel function in transcriptional control.
Received for publication, June 16, 2003 , and in revised form, October 19, 2003.
* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains tables and additional figures.
¶ To whom correspondence should be addressed: Dept. of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Helmholtzstr. 20, D-89081 Ulm, Germany. Tel.: 49-731-500-24281; Fax: 49-731-500-24299; E-mail: ladislav.burysek{at}medizin.uni-ulm.de.
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