Analysis of the effects of importin 1 on the nuclear translocation of IL-1 in HeLa cells

Interleukin-1 alpha (IL-1 alpha), a cytokine released by necrotic cells, causes sterile inflammation. On the other hand, IL-1 alpha is present in the nucleus and also regulates the expression of many proteins. A protein substrate containing a classical nuclear localization signal (cNLS) typically forms a substrate/importin alpha/beta complex, which is subsequently transported to the nucleus. To the best of our knowledge, no study has directly investigated whether IL-1 alpha-which includes cNLS-is imported into the nucleus in an importin alpha/beta-dependent manner. In this study, we noted that all detected importin alpha subtypes interacted with IL-1 alpha. In HeLa cells, importin alpha 1-mediated nuclear translocation of IL-1 alpha occurred at steady state and was independent of importin beta 1. Importin alpha 1 not only was engaged in IL-1 alpha nuclear transport but also concurrently functioned as a molecule that regulated IL-1 alpha protein level in the cell. Furthermore, we discussed the underlying mechanism of IL-1 alpha nuclear translocation by importin alpha 1 based on our findings.