Notch1 confers a resistance to glucocorticoid-induced apoptosis on developing thymocytes by down-regulating SRG3 expression

被引:29
作者
Choi, YI
Jeon, SH
Jang, J
Han, S
Kim, JK
Chung, H
Lee, HW
Chung, HY
Park, SD
Seong, RH
机构
[1] Seoul Natl Univ, Inst Mol Biol & Genet, Kwanak Gu, Seoul 151742, South Korea
[2] Seoul Natl Univ, Sch Biol Sci, Kwanak Gu, Seoul 151742, South Korea
[3] Int Vaccine Inst, Seoul 151742, South Korea
[4] Sungkyunkwan Univ, Sch Med, Dept Mol Cell Biol, Suwon 440746, South Korea
[5] Samsung Biomed Res Inst, Suwon 440746, South Korea
[6] Hanyang Univ, Sch Med, Dept Microbiol, Seoul 133791, South Korea
关键词
D O I
10.1073/pnas.181076198
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We previously have reported that SRG3 is required for glucocorticoid (GC)-induced apoptosis in the S49.1 thymoma cell line. Activation of Notch1 was shown to induce GC resistance in thymocytes. However, the specific downstream target of Notch1 that confers GC resistance on thymocytes is currently unknown. We found that the expression level of SRG3 was critical in determining GC sensitivity in developing thymocytes. The expression of SRG3 also was down-regulated by the activated form of Notch1 (NotchIC). The promoter activity of the SRG3 gene also was downregulated by NotchIC. Expression of transgenic SRG3 resulted in the restoration of GC sensitivity in thymocytes expressing transgenic Notch1. These results suggest that SRG3 is the downstream target of Notch1 in regulating GC sensitivity of thymocytes.
引用
收藏
页码:10267 / 10272
页数:6
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