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interacts with elements of the RNA processing apparatus and induces apoptosis in malignant cells
1
* The Department of Medicine, University of California, San Francisco, Northern California Institute for Research and Education, Veterans Administration Medical Center and
UCSF Comprehensive Cancer Center, San Francisco, California, USA
1Correspondence: Department of Medicine (111J), San Francisco VAMC, 4150 Clement St., San Francisco, CA 94121, USA. E-mail: pollock.allan{at}maelstrom.ucsf.edu
Interleukin 1
(IL-1), a 33 kDa precursor, is cleaved releasing the 17 kDa carboxyl-terminal cytokine IL-1 to which all of the biological properties of IL-1 have been attributed. We investigated the potential independent properties of the remaining 16 kDa IL-1 amino-terminal propiece by expression in human tumor and primary human cell lines. The IL-1 propiece produced apoptosis in malignant but not normal cell lines. A minimal fragment comprised of amino acids 55–108 was required for apoptosis. Deletion and mutation studies identified an extended nuclear localization sequence required for nuclear localization, induction of apoptosis and concentration of the IL-1 propiece in interchromatin granule clusters, concentrations of proteins in the RNA splicing and processing pathways. The IL-1 propiece interacted with five known components of the RNA splicing/processing pathway, suggesting that the mechanism of action may involve changes in RNA splicing or processing. Expression of the IL-1 propiece caused a shift in the ratio of Bcl-Xl/Bcl-Xs toward the apoptotic direction. Our findings indicate that the IL-1 propiece induces apoptosis in a range of tumor cells and likely operates through a mechanism involving the RNA processing apparatus and the alternate splicing of apoptosis regulatory proteins.—Pollock, A. S., Turck, J., Lovett, D. H. The prodomain of interleukin-1 interacts with elements of the RNA processing apparatus and induces apoptosis in malignant cells.
Key Words: IL-1 • nuclear localization signal • RNA processing • Bcl-X
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