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Chromosome 22 complements apoptosis in Fas-and TNF-resistant mutant UK110 cells

K Noguchi1, M Naito, M Oshimura

  • 1Laboratory of Biomedical Research, Institute of Molecular and Cellular Biosciences, University of Tokyo.

Oncogene
|July 4, 1996
PubMed

Insights

Chromosome 22 restores apoptosis sensitivity in resistant leukemia cells. This suggests a gene on chromosome 22 is crucial for Fas and tumor necrosis factor receptor (TNFR) signaling upstream of key proteases.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Fas and p55 tumor necrosis factor receptor (TNFR) mediate apoptosis upon activation.
  • The precise signal transduction pathway for Fas and p55 TNFR-induced apoptosis remains unclear.
  • A recessive mutant cell line, UK110, derived from U937 leukemia cells, exhibits resistance to Fas and p55 TNFR-mediated apoptosis.

Purpose of the Study:

  • To elucidate the signal transduction mechanism of apoptosis via Fas and p55 TNFR.
  • To identify genetic factors involved in Fas and p55 TNFR-mediated apoptosis resistance.
  • To investigate the role of chromosome 22 in restoring apoptosis sensitivity.

Main Methods:

  • Cytogenetic analysis of the UK110 mutant cell line.
  • Microcell-fusion technique to introduce chromosome 22 into UK110 cells.
  • Assessment of apoptosis sensitivity following treatment with anti-Fas and anti-p55 TNFR antibodies.
  • Evaluation of interleukin-1 beta converting enzyme (ICE)-like protease processing.

Main Results:

  • Introduction of chromosome 22 specifically restored sensitivity to Fas- and TNF-mediated apoptosis in UK110 cells.
  • Chromosome 22 introduction complemented the processing of ICE-like proteases (CPP32/Yama/Apopain and ICH-1L) after antibody treatment.
  • These findings indicate a gene on chromosome 22 is involved upstream of ICE-like proteases in the apoptosis pathway.

Conclusions:

  • A gene located on human chromosome 22 plays a critical role in the Fas and p55 TNFR apoptotic signaling pathway.
  • This gene acts upstream of ICE-like proteases, influencing their activation.
  • Restoring chromosome 22 can overcome apoptosis resistance in certain leukemia cells, offering potential therapeutic insights.

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