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 PCAF⅐p300 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.

identified the previously unreported interaction of IL-1α with the tumor suppressor p53 in both malignant and noncancerous mammalian cell lines and provide evidence that IL-1α can closely colocalize with p53 in both the nucleus and cytoplasm of mammalian cells. Furthermore, this interaction was enhanced by treatment with the DNA-damaging drug etoposide. Results p53 and IL-1α colocalize in both the cell nucleus and cytoplasm. To analyze the subcellular distribution of IL-1α and p53 in mammalian cells and their potential to colocalize, we employed the A375 human malignant melanoma cell line. Endogenous proteins were observed using indirect immunofluorescence and confocal microscopy. Whereas a nuclear distribution of IL-1α and p53 was predominant in our experiments, some signal corresponding to these proteins was regularly detected in the cytoplasm. Data analysis using the ImageJ RGB profiler plugin suggested that a fraction of the p53 and IL-1α populations colocalize in certain regions (Fig. 1). The Pearson's colocalization coefficient computed using the Coloc2 Fiji plugin also suggested the modest colocalization (r = 0.464) of both proteins. We observed the similar behavior of both proteins in the HeLa human cervical cancer cell line and U2OS human osteosarcoma cell line as well (Supplementary Fig. 1).

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