Aggregation of Thy-1 glycoprotein induces thymocyte apoptosis through activation of CPP32-like proteases

被引:15
|
作者
Fujita, N
Kodama, N
Kato, Y
Lee, SH
Tsuruo, T
机构
[1] UNIV TOKYO,INST MOL & CELLULAR BIOSCI,BIOMED RES LAB,BUNKYO KU,TOKYO 113,JAPAN
[2] JAPANESE FDN CANC RES,CTR CANC CHEMOTHERAPY,TOSHIMA KU,TOKYO 170,JAPAN
关键词
D O I
10.1006/excr.1997.3505
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Mouse thymocytes are known to undergo apoptosis by ligating some unique anti Thy-1 monoclonal antibodies (mAbs), G7 and KT16. However, the precise mechanisms of Thy-1-mediated apoptosis are as yet unclear. We investigated Thy-1-mediated apoptosis using our previously generated anti-Thy-1 mAb, MCS-34, which was similar to G7 because both antibodies rec ognized both Thy-1.1 and Thy-1.2 and bound Thy-1A epitope. Unlike G7, MCS-34 alone could not induce apoptosis in thymocytes; however, it could induce apoptosis when it was cross-linked with second antibodies. Thus, MCS-34 could not aggregate by itself, but G7 could. In the course of investigating the apoptosis-related molecules that were involved in the thymocyte apoptosis induced by cross-linking of MCS-34 or by G7 ligation, we found that CPP32-like proteases were activated during the apoptosis. Furthermore, the expression of bcl-2 and bcl-X-L proteins was decreased in these apoptosis processes. Whereas the ligation of MCS-34 alone could not generate apoptosis signals that led to the activation of CPP32-like proteases and the decrease in bcl-2 and bcl-X-L expression, the aggregation of Thy-1 glycoprotein might be crucial to signal thymocyte apoptosis. These results indicate that MCS-34 is a useful anti-Thy-1 mAb for analyzing the Thy-1-mediated signals since MCS-34 can control the level of apoptosis by using second antibodies. (C) 1997 Academic Press.
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页码:400 / 406
页数:7
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