Intracellular interleukin-1alpha functionally interacts with histone acetyltransferase complexes.
Interleukin-1alpha (IL-1alpha) is an inflammatory cytokine acting extracellularly via membrane receptors. Interestingly, a significant portion of synthesized IL-1alpha is not secreted; instead, it is actively translocated into the cell nucleus. IL-1alpha 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-1alpha 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-1alpha 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-1alpha precursor and suggest its novel function in transcriptional control.
Buryskova
Miroslava
M
Department of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, D-89081 Ulm, Germany.
Pospisek
Martin
M
Grothey
Arnhild
A
Simmet
Thomas
T
Burysek
Ladislav
L
D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006801:Humans; D007375:Interleukin-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D007375:Interleukin-1; D009097:Multienzyme Complexes; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C052130:GAL4 protein, S cerevisiae