Proapoptotic activity of ITM2B(s), a BH3-only protein induced upon IL-2-deprivation which interacts with Bcl-2

Oncogene. 2002 May 9;21(20):3181-9. doi: 10.1038/sj.onc.1205464.


Growth factor deprivation is a physiological mechanism to induce apoptosis. We used an IL-2-dependent murine T cell line to identify proteins that trigger apoptosis. Here we report the identification, the cloning and characterization of ITM2B(s), a protein induced upon IL-2-deprivation. ITM2B(s), which shares the BH3 domain of Bcl-2 family members, is a cytoplasmic and mitochondrial protein. Expression of ITM2B(s) induces apoptosis in IL-2-stimulated cells, but not in IL-4-stimulated cells, while overexpression of the long form of the protein is not able to induce apoptosis. In IL-2-stimulated cells, ITM2B(s) interacts with the antiapoptotic protein Bcl-2, and does not interact with the proapoptotic Bad. Mutation of the critical L and D residues within the BH3 domain abolished the ability of ITM2B(s) to promote apoptosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alternative Splicing
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Apoptosis / physiology*
  • Carrier Proteins / metabolism
  • Cell Line / drug effects
  • Cell Line / metabolism
  • Cloning, Molecular
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Interleukin-2 / pharmacology*
  • Macromolecular Substances
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Recombinant Fusion Proteins / physiology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Subtraction Technique
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • Transfection
  • bcl-Associated Death Protein


  • Adaptor Proteins, Signal Transducing
  • Bad protein, mouse
  • Carrier Proteins
  • Interleukin-2
  • Itm2b protein, mouse
  • Macromolecular Substances
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • bcl-Associated Death Protein