期刊
FASEB JOURNAL
卷 17, 期 2, 页码 203-213出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.02-0602com
关键词
IL-1 alpha; nuclear localization signal; RNA processing; Bcl-X
资金
- NCI NIH HHS [R55 CA91038] Funding Source: Medline
- NIDDK NIH HHS [R01DK39776, R01DK31398] Funding Source: Medline
Interleukin 1alpha (IL-1alpha), a 33 kDa precursor, is cleaved releasing the 17 kDa carboxyl-terminal cytokine IL-1alpha to which all of the biological properties of IL-1alpha have been attributed. We investigated the potential independent properties of the remaining 16 kDa IL-1alpha amino-terminal propiece by expression in human tumor and primary human cell lines. The IL-1alpha 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-1alpha propiece in interchromatin granule clusters, concentrations of proteins in the RNA splicing and processing pathways. The IL-1alpha 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-1alpha propiece caused a shift in the ratio of Bcl-X-1/Bcl-X-s toward the apoptotic direction. Our findings indicate that the IL-1alpha 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.
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