Noguchi K, Naito M, Oshimura M, Mashima T, Fujita N, Yonehara S, Tsuruo T
Laboratory of Biomedical Research, Institute of Molecular and Cellular Biosciences, University of Tokyo.
Oncogene. 1996 Jul 4;13(1):39-46.
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.
Fas和p55肿瘤坏死因子受体（TNFR）在与它们的配体或激动性抗体交联时传递凋亡信号。然而，通过Fas和p55 TNFR介导凋亡的信号转导机制尚未阐明。我们先前描述了来自人单核细胞白血病U937细胞系的一个隐性突变体UK110，它对Fas和p55 TNFR介导的凋亡具有抗性。通过细胞遗传学分析和微细胞融合方法，我们在此证明导入22号染色体可特异性恢复UK110细胞对Fas和TNF介导凋亡的敏感性。此外，在用抗Fas和抗p55 TNFR抗体处理后，将22号染色体导入UK110可补充白细胞介素-1β转化酶（ICE）样蛋白酶如CPP32/Yama/Apopain和ICH-1L的加工过程。这些结果表明位于22号染色体上的一个基因的产物在ICE样蛋白酶的上游某个点参与Fas和p55 TNFR介导的凋亡。
