The N-terminal propiece of interleukin 1 alpha is a transforming nuclear oncoprotein

Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):508-13. doi: 10.1073/pnas.94.2.508.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Compartmentation
  • Cytosol / metabolism
  • Fluorescent Antibody Technique, Indirect
  • Interleukin-1 / chemistry*
  • Kidney Glomerulus
  • Molecular Sequence Data
  • Nuclear Proteins / physiology*
  • Peptide Fragments
  • Proto-Oncogene Proteins / chemistry*
  • Rats

Substances

  • Interleukin-1
  • Nuclear Proteins
  • Peptide Fragments
  • Proto-Oncogene Proteins