Endogenous interleukin 1 alpha must be transported to the nucleus to exert its activity in human endothelial cells.
Copyright policy )Endogenous interleukin 1 alpha must be transported to the nucleus to exert its activity in human endothelial cells.
We have previously shown that the signal peptideless cytokine interleukin 1 alpha (IL-1 alpha) may play a role as an intracellular regulator of human endothelial cell senescence (J. A. M. Maier, P. Voulalas, D. Roeder, and T. Maciag, Science 249:1570-1574, 1990). To investigate the potential intracellular function of IL-1 alpha, transformed endothelial cells were transfected with the human cDNAs that code for the two forms of IL-1 alpha, the precursor molecule IL-1(1-271) and the mature protein IL-1(113-271). The subcellular localization of the two different polypeptides was investigated directly or by using chimeric genes constructed by fusion of different fragments of the IL-1 alpha gene and the beta-galactosidase open reading frames. The IL-1(113-271) protein was cytoplasmic, while IL-1(1-271) was nuclear. The basic cluster at the NH2 terminus of IL-1, KVLKKRR, has been shown to mediate IL-1 alpha nuclear targeting. Moreover, nuclear localization of IL-1 alpha correlates with impaired cell growth and expression of some IL-1 alpha-inducible genes. These results suggest that transport of endogenous IL-1(1-271) into the nucleus is required for it to modulate endothelial cell function.
- University of Milan Italy
Cell Nucleus, Base Sequence, Molecular Sequence Data, Fluorescent Antibody Technique, Biological Transport, Recombinant Proteins; Humans; Biological Transport; Cell Nucleus; Collagenases; Endothelium, Vascular; RNA, Messenger; Base Sequence; Gene Expression Regulation, Enzymologic; Interleukin-1; Transfection; Cells, Cultured; Cell Compartmentation; DNA Primers; Plasminogen Activator Inhibitor 1; Molecular Sequence Data; Fluorescent Antibody Technique; Cell Division, In Vitro Techniques, Transfection, Gene Expression Regulation, Enzymologic, Recombinant Proteins, Cell Compartmentation, Plasminogen Activator Inhibitor 1, Humans, Collagenases, Endothelium, Vascular, RNA, Messenger, Cell Division, Cells, Cultured, DNA Primers, Interleukin-1
Cell Nucleus, Base Sequence, Molecular Sequence Data, Fluorescent Antibody Technique, Biological Transport, Recombinant Proteins; Humans; Biological Transport; Cell Nucleus; Collagenases; Endothelium, Vascular; RNA, Messenger; Base Sequence; Gene Expression Regulation, Enzymologic; Interleukin-1; Transfection; Cells, Cultured; Cell Compartmentation; DNA Primers; Plasminogen Activator Inhibitor 1; Molecular Sequence Data; Fluorescent Antibody Technique; Cell Division, In Vitro Techniques, Transfection, Gene Expression Regulation, Enzymologic, Recombinant Proteins, Cell Compartmentation, Plasminogen Activator Inhibitor 1, Humans, Collagenases, Endothelium, Vascular, RNA, Messenger, Cell Division, Cells, Cultured, DNA Primers, Interleukin-1
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