ABCB3 p.Arg175His
| Predicted by SNAP2: | A: D (59%), C: N (53%), D: D (71%), E: N (53%), F: D (66%), G: D (63%), H: N (53%), I: D (63%), K: N (82%), L: D (63%), M: D (53%), N: D (53%), P: D (75%), Q: N (82%), S: D (53%), T: D (53%), V: D (63%), W: D (75%), Y: D (66%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: D, P: D, Q: N, S: D, T: D, V: D, W: D, Y: D, |
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[hide] p53 induces TAP1 and enhances the transport of MHC... Oncogene. 1999 Dec 16;18(54):7740-7. Zhu K, Wang J, Zhu J, Jiang J, Shou J, Chen X
p53 induces TAP1 and enhances the transport of MHC class I peptides.
Oncogene. 1999 Dec 16;18(54):7740-7., [PMID:10618714]
Abstract [show]
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.
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No. Sentence Comment
89 In contrast, the luciferase activity for TAP1-Fluc was not increased by the mutants p53(V143A), p53(R175H), p53(R249S), or p53(R273H) (Figure 5c), consistent with the observation that mutant p53(R249S) was incapable of inducing TAP1 (Figure 1a).
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ABCB3 p.Arg175His 10618714:89:100
status: NEW95 5 mg of TAP1-Fluc was co-transfected into H1299 cells with 5 mg of pcDNA3 or a vector that expresses p53(V143A), p53(R175H), p53(R249S), or p53(R273H).
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ABCB3 p.Arg175His 10618714:95:117
status: NEW190 TAP1-Fluc or GADD45-Fluc was co-transfected into H1299 cells with control vector pcDNA3 or a vector that expresses wild-type p53, p53(V143A), p53(R175H), p53(R249S), p53(R273H), p73a or p73b.
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ABCB3 p.Arg175His 10618714:190:146
status: NEW[hide] Upregulation of major histocompatibility complex c... J Virol. 2003 Aug;77(15):8299-309. Herzer K, Falk CS, Encke J, Eichhorst ST, Ulsenheimer A, Seliger B, Krammer PH
Upregulation of major histocompatibility complex class I on liver cells by hepatitis C virus core protein via p53 and TAP1 impairs natural killer cell cytotoxicity.
J Virol. 2003 Aug;77(15):8299-309., [PMID:12857899]
Abstract [show]
The mechanisms of immune evasion and the role of the early immune response in chronic infection caused by hepatitis C virus (HCV) are still unclear. Here, we present evidence for a cascade of molecular events that the virus initiates to subvert the innate immune attack. The HCV core protein induced p53-dependent gene expression of TAP1 (transporter associated with antigen processing 1) and consecutive major histocompatibility complex (MHC) class I upregulation. Moreover, in p53-deficient liver cell lines, only reconstitution with wild-type p53, but not mutated p53 lacking DNA binding capacity, showed this effect. As a consequence of increased MHC class I expression, a significantly downregulated cytotoxic activity of natural killer (NK) cells against HCV core-transfected liver cells was observed, whereas lysis by HCV-specific cytotoxic T cells was not affected. These results demonstrate a way in which HCV avoids recognition by NK cells that may contribute to the establishment of a chronic infection.
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No. Sentence Comment
177 Luciferase activity was not increased upon cotransfection of mutant p53(R175H), which contains a defect in the DNA-binding domain (Fig. 3C).
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ABCB3 p.Arg175His 12857899:177:72
status: NEW199 Hep3B and Huh7 cells (both p53afa; ) were cotransfected with TAP1-Luc, decreasing amounts of HCV core expression vector, the empty expression vector to adjust for equal amounts of DNA, WTp53, or p53(R175H), as indicated.
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ABCB3 p.Arg175His 12857899:199:202
status: NEW203 Hep3B and Huh7 cells were transfected with expression plasmids for WTp53, p53(R175H), or the HCV core protein alone or in combination as indicated.
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ABCB3 p.Arg175His 12857899:203:78
status: NEW208 served upregulation of TAP1, also MHC class I expression was increased in response to HCV core protein in the presence of WTp53 but not in the presence of p53(R175H) (Fig. 4).
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ABCB3 p.Arg175His 12857899:208:159
status: NEW333 Finally, we may be able to take advantage of this knowledge for vaccine development or specific immunotherapy. ACKNOWLEDGMENTS We are grateful to M. Oren for providing expression plasmids WTp53 and p53(R175H), to B. Vogelstein for pG13-Luc and tools for adenovirus constructs, to E. Klar and T. Lehnert for making human liver tissue available, to R. Bartenschlager and T. Pietschmann for providing antibodies, to D. Koppenho &#a8;fer, M. Pach, and B. Mosetter for excellent technical assistance, and to A. Krueger and M. Sprick for critical review of the manuscript.
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ABCB3 p.Arg175His 12857899:333:202
status: NEW