p53 induces TAP1 and enhances the transport of MHC class I peptides.
The transporter associated with antigen processing (TAP) 1 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, we 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.
Zhu
K
K
Institute of Molecular Medicine, Medical College of Georgia, Augusta, Georgia, GA 30912, USA.
Wang
J
J
Zhu
J
J
Jiang
J
J
Shou
J
J
Chen
X
X
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016158:Genes, p53; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; C073119:TAP1 protein, human; D016159:Tumor Suppressor Protein p53