title: The N-terminal propiece of interleukin 1 alpha is a transforming nuclear oncoprotein.
abstract: Interleukin 1 alpha (IL-1 alpha) is a pleiotropic cytokine involved in the immune response, inflammatory processes, and hematopoiesis, and acts as a mitogen for several malignant cell types, including acute leukemia and Kaposi sarcoma cells. These diverse activities have been exclusively attributed to the plasma membrane receptor-binding, 17-kDa C-terminal component (mature IL-1 alpha) that results from proteolytic processing of the 31- to 33-kDa precursor protein. No biologic function has been ascribed to the unusually large, 16-kDa N-terminal propiece formed as a result of proteolytic processing of IL-1 alpha. We report that the IL-1 alpha N-terminal propiece is concentrated by means of a nuclear localization sequence within the nuclei of both transfected and leukemic cell lines. Overexpression of this component in glomerular mesangial cells, a model perivascular myofibroblast cell type capable of IL-1 alpha synthesis and processing, results in malignant transformation to a spindle cell-type tumor. The functionally bipartite nature of the IL-1 alpha precursor represents a unique combination of the C-terminal, classical cytokine and an N-terminal nuclear oncoprotein. These findings suggest that nuclear transport of the IL-1 alpha N-terminal component may represent a critical component in the transformation of IL-1 alpha-producing cells in the bone marrow or the perivascular area to a malignant phenotype.
authors.affiliation: Department of Medicine, University of California, Davis, Sacramento 95817, USA.
authors.forename: F T
authors.initials: FT
authors.lastname: Stevenson
authors.forename: J
authors.initials: J
authors.lastname: Turck
authors.forename: R M
authors.initials: RM
authors.lastname: Locksley
authors.forename: D H
authors.initials: DH
authors.lastname: Lovett
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002451:Cell Compartmentation; D003600:Cytosol / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D007375:Interleukin-1 / Q000737:chemistry*; D007678:Kidney Glomerulus; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins / Q000737:chemistry*; D051381:Rats
chemical_list: D007375:Interleukin-1; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins