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

ABSTRACT

Fas and p55 tumor necrosis factor receptor (TNFR) transfer an apoptosis signal when they are crosstinked with their ligands or agonistic antibodies. However, the signal transduction mechanism of apoptosis via Fas and p55 TNFR has not yet been elucidated. We previously described a recessive mutant UK110 from the human monocytic leukemia U937 cell line, that showed resistance against Fas- and p55 TNFR-mediated apoptosis. By cytogenetic analysis and microcell-fusion method, we demonstrate here that introduction of chromosome 22 can specifically restore the sensitivity to Fas- and TNF-mediated apoptosis in UK110 cells. Moreover, introduction of chromosome 22 into UK110 can complement the processing of interleukin-1 beta converting enzyme (ICE)-like proteases, such as CPP32/Yama/Apopain and ICH-1L, after treatment with anti-Fas and anti-p55 TNFR antibodies. These results suggest that the product of a gene located on chromosome 22 participates in the Fas-and p55 TNFR-mediated apoptosis at a point upstream of ICE-like proteases.