p53 induces TAP1 and enhances the transport of MHC class I peptides

被引:94
作者
Zhu, KC [1 ]
Wang, J [1 ]
Zhu, JH [1 ]
Jiang, JY [1 ]
Shou, J [1 ]
Chen, XB [1 ]
机构
[1] Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA
关键词
p53; TAP1; MHC class I; interferon gamma; tumor surveillance;
D O I
10.1038/sj.onc.1203235
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The transporter associated with antigen processing (TAP) I is required for the major histocompatibility complex (MHC) class I antigen presentation pathway, which plays a key role in host tumor surveillance. Since more than 50% of tumors have a dysfunctional p53, evasion of tumor surveillance by tumor cells may be linked to loss of p53 function. Here we found that TAP1 is strongly induced by p53 and DNA-damaging agents through a p53-responsive element. We also found that p73, which is homologous to p53, is capable of inducing TAP1 and cooperates with p53 to activate TAP1. Furthermore, me found that by inducing TAP1, p53 enhances the transport of MHC class I peptides and expression of surface MHC-peptide complexes, and cooperates with interferon gamma to activate the MHC class I pathway. These results suggest that tumor surveillance may be a mechanism by which p53 and/or p73 function as tumor suppressors.
引用
收藏
页码:7740 / 7747
页数:8
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