p53 induces TAP1 and enhances the transport of MHC class I peptides
p53 induces TAP1 and enhances the transport of MHC class I peptides
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DOI：
10.1038/sj.onc.1203235
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发表时间：
1999-12-16
期刊：
影响因子：
8
通讯作者：
Chen, XB
中科院分区：
文献类型：
--
作者：
Zhu, KC;Wang, J;Chen, XB
抗原加工相关转运蛋白（TAP） I是主要组织相容性复合体（MHC） I类抗原递呈途径所必需的，在宿主肿瘤监测中起关键作用。由于超过50%的肿瘤具有功能失调的p53，肿瘤细胞逃避肿瘤监测可能与p53功能丧失有关。在这里，我们发现TAP1通过p53应答元件被p53和dna损伤剂强烈诱导。我们还发现，与p53同源的p73能够诱导TAP1，并与p53合作激活TAP1。此外，我发现p53通过诱导TAP1增强MHC I类肽的转运和表面MHC肽复合物的表达，并与干扰素γ协同激活MHC I类通路。这些结果表明，肿瘤监测可能是p53和/或p73作为肿瘤抑制因子的一种机制。
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.