Dendritic cell IL-1α and IL-1β are polyubiquitinated and degraded by the proteasome.

Joseph Ainscough, G. Frank Gerberick, Maryam Zahedi-Nejad, Gloria Lopez-Castejon, David Brough, Ian Kimber, Rebecca J Dearman

    Research output: Contribution to journalArticlepeer-review


    IL-1α and β are key players in the innate immune system. The secretion of these cytokines by dendritic cells (DC) is integral to the development of proinflammatory responses. These cytokines are not secreted via the classical secretory pathway. Instead, 2 independent processes are required; an initial signal to induce up-regulation of the precursor pro-IL-1α and -β, and a second signal to drive cleavage and consequent secretion. Pro-IL-1α and -β are both cytosolic and thus, are potentially subject to post-translational modifications. These modifications may, in turn, have a functional outcome in the context of IL-1α and -β secretion and hence inflammation. We report here that IL-1α and -β were degraded intracellularly in murine bone marrow-derived DC and that this degradation was dependent on active cellular processes. In addition, we demonstrate that degradation was ablated when the proteasome was inhibited, whereas autophagy did not appear to play a major role. Furthermore, inhibition of the proteasome led to an accumulation of polyubiquitinated IL-1α and -β, indicating that IL-1α and -β were polyubiquitinated prior to proteasomal degradation. Finally, our investigations suggest that polyubiquitination and proteasomal degradation are not continuous processes but instead are up-regulated following DC activation. Overall, these data highlight that IL-1α and -β polyubiquitination and proteasomal degradation are central mechanisms in the regulation of intracellular IL-1 levels in DC.
    Original languageEnglish
    Pages (from-to)35582-35592
    Number of pages11
    JournalJournal of Biological Chemistry
    Issue number51
    Publication statusPublished - 19 Dec 2014


    • Dendritic Cell
    • IL-1α IL-1β
    • Inflammation
    • Interleukin 1 (IL-1)
    • Proteasome
    • Ubiquitylation (Ubiquitination)

    Research Beacons, Institutes and Platforms

    • Dementia@Manchester


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