Presence of a Cytoplasmic Retention Sequence within the Human Interleukin-1α Precursor

Interleukin (IL)-1alpha is primarily translated as a 33 kDa molecule (IL-1alpha1-271), and then processed into a 17 kDa molecule (IL-1alpha119-271) by calpain. The precursor region of IL-1alpha (IL-1 alpha1-118) contains a nuclear localization signal (KVLKKRRL, residues 79-86). We investigated the intracellular localization of IL-1alpha fused with green fluorescent protein or beta-galactosidase. IL-1alpha1-118 was localized exclusively in the nucleus, but IL-1 alpha1-271 in both the nucleus and the cytoplasm, suggesting the presence of a cytoplasmic retention signal within the mature region of IL-1alpha. Furthermore, the intracellular localization of IL-1alpha with deletions from the C terminus, internal deletions and point mutations suggested that the cytoplasmic retention signal is located within residues 168-201.