Interleukin-1α associates with the tumor suppressor p53 following DNA damage

Abstract

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).

AAV vectors trigger DNA damage responses and STING-dependent inflammation in human CNS cells

“…Moreover, the duration of the insult, which is not easy to predict in vitro, will be important to consider in the development of protocols based on transient immunomodulation. Links between IL-1 signaling and p53 have been reported in the context of tumor cells 45,46 , and the cGAS-STING axis is increasingly linked to DNA damage 47 , although the exact triggers of this pathway in the context of AAV-mediated CNS transduction remain to be de ned. Interestingly, the cGAS-STING signaling axis has been recently shown to drive chronic in ammation and functional decline during ageing in mice, with neuroprotective effects achieved using the H151 inhibitor 48 .…”

In Situ Detection of Complex DNA Damage Using Microscopy: A Rough Road Ahead

“…In the Proximity Ligation Assay (PLA), a fluorescent signal is produced only when the molecules of interest are located in close proximity. In this case, the secondary antibodies, i.e., PLA probes, are not fluorescent by themselves, but they carry single stranded oligonucleotides that can synthesize fluorescent macromolecule in the simultaneous presence of the target enzymes [44,[72][73][74]. PLA in principle works when the proteins of interest are located in distances smaller than 40 nm, making it a competitive assay in terms of complex DNA damage detection.…”