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2fo4

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[[Image:2fo4.png|left|200px]]
 
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{{STRUCTURE_2fo4| PDB=2fo4 | SCENE= }}
{{STRUCTURE_2fo4| PDB=2fo4 | SCENE= }}
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===Enhanced MHC class I binding and immune responses through anchor modification of the non-canonical tumor associated MUC1-8 peptide===
===Enhanced MHC class I binding and immune responses through anchor modification of the non-canonical tumor associated MUC1-8 peptide===
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{{ABSTRACT_PUBMED_17067310}}
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{{ABSTRACT_PUBMED_17067310}}
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==Disease==
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[[http://www.uniprot.org/uniprot/MUC1_HUMAN MUC1_HUMAN]] Note=MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed:20816948). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes.
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==Function==
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[[http://www.uniprot.org/uniprot/HA1B_MOUSE HA1B_MOUSE]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/MUC1_HUMAN MUC1_HUMAN]] The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.<ref>PMID:9139698</ref><ref>PMID:11877440</ref><ref>PMID:14688481</ref><ref>PMID:15710329</ref><ref>PMID:16288032</ref><ref>PMID:15513966</ref><ref>PMID:17524503</ref><ref>PMID:17308127</ref><ref>PMID:16983337</ref> The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity.<ref>PMID:9139698</ref><ref>PMID:11877440</ref><ref>PMID:14688481</ref><ref>PMID:15710329</ref><ref>PMID:16288032</ref><ref>PMID:15513966</ref><ref>PMID:17524503</ref><ref>PMID:17308127</ref><ref>PMID:16983337</ref> [[http://www.uniprot.org/uniprot/B2MG_MOUSE B2MG_MOUSE]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
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<ref group="xtra">PMID:017067310</ref><references group="xtra"/>
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<ref group="xtra">PMID:017067310</ref><references group="xtra"/><references/>
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Lazoura, E.]]
[[Category: Lazoura, E.]]

Revision as of 17:25, 24 March 2013

Template:STRUCTURE 2fo4

Contents

Enhanced MHC class I binding and immune responses through anchor modification of the non-canonical tumor associated MUC1-8 peptide

Template:ABSTRACT PUBMED 17067310

Disease

[MUC1_HUMAN] Note=MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed:20816948). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes.

Function

[HA1B_MOUSE] Involved in the presentation of foreign antigens to the immune system. [MUC1_HUMAN] The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.[1][2][3][4][5][6][7][8][9] The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity.[10][11][12][13][14][15][16][17][18] [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.

About this Structure

2fo4 is a 3 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA.

See Also

Reference

  • Lazoura E, Lodding J, Farrugia W, Ramsland PA, Stevens J, Wilson IA, Pietersz GA, Apostolopoulos V. Enhanced major histocompatibility complex class I binding and immune responses through anchor modification of the non-canonical tumour-associated mucin 1-8 peptide. Immunology. 2006 Nov;119(3):306-16. PMID:17067310 doi:10.1111/j.1365-2567.2006.02434.x
  1. Yamamoto M, Bharti A, Li Y, Kufe D. Interaction of the DF3/MUC1 breast carcinoma-associated antigen and beta-catenin in cell adhesion. J Biol Chem. 1997 May 9;272(19):12492-4. PMID:9139698
  2. Ren J, Li Y, Kufe D. Protein kinase C delta regulates function of the DF3/MUC1 carcinoma antigen in beta-catenin signaling. J Biol Chem. 2002 May 17;277(20):17616-22. Epub 2002 Mar 4. PMID:11877440 doi:10.1074/jbc.M200436200
  3. Huang L, Ren J, Chen D, Li Y, Kharbanda S, Kufe D. MUC1 cytoplasmic domain coactivates Wnt target gene transcription and confers transformation. Cancer Biol Ther. 2003 Nov-Dec;2(6):702-6. PMID:14688481
  4. Wei X, Xu H, Kufe D. Human MUC1 oncoprotein regulates p53-responsive gene transcription in the genotoxic stress response. Cancer Cell. 2005 Feb;7(2):167-78. PMID:15710329 doi:10.1016/j.ccr.2005.01.008
  5. Huang L, Chen D, Liu D, Yin L, Kharbanda S, Kufe D. MUC1 oncoprotein blocks glycogen synthase kinase 3beta-mediated phosphorylation and degradation of beta-catenin. Cancer Res. 2005 Nov 15;65(22):10413-22. PMID:16288032 doi:65/22/10413
  6. Mukherjee P, Tinder TL, Basu GD, Gendler SJ. MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and normal T cells. J Leukoc Biol. 2005 Jan;77(1):90-9. Epub 2004 Oct 28. PMID:15513966 doi:jlb.0604333
  7. Lillehoj EP, Lu W, Kiser T, Goldblum SE, Kim KC. MUC1 inhibits cell proliferation by a beta-catenin-dependent mechanism. Biochim Biophys Acta. 2007 Jul;1773(7):1028-38. Epub 2007 Apr 22. PMID:17524503 doi:S0167-4889(07)00092-4
  8. Wei X, Xu H, Kufe D. Human mucin 1 oncoprotein represses transcription of the p53 tumor suppressor gene. Cancer Res. 2007 Feb 15;67(4):1853-8. PMID:17308127 doi:67/4/1853
  9. Pochampalli MR, el Bejjani RM, Schroeder JA. MUC1 is a novel regulator of ErbB1 receptor trafficking. Oncogene. 2007 Mar 15;26(12):1693-701. Epub 2006 Sep 18. PMID:16983337 doi:1209976
  10. Yamamoto M, Bharti A, Li Y, Kufe D. Interaction of the DF3/MUC1 breast carcinoma-associated antigen and beta-catenin in cell adhesion. J Biol Chem. 1997 May 9;272(19):12492-4. PMID:9139698
  11. Ren J, Li Y, Kufe D. Protein kinase C delta regulates function of the DF3/MUC1 carcinoma antigen in beta-catenin signaling. J Biol Chem. 2002 May 17;277(20):17616-22. Epub 2002 Mar 4. PMID:11877440 doi:10.1074/jbc.M200436200
  12. Huang L, Ren J, Chen D, Li Y, Kharbanda S, Kufe D. MUC1 cytoplasmic domain coactivates Wnt target gene transcription and confers transformation. Cancer Biol Ther. 2003 Nov-Dec;2(6):702-6. PMID:14688481
  13. Wei X, Xu H, Kufe D. Human MUC1 oncoprotein regulates p53-responsive gene transcription in the genotoxic stress response. Cancer Cell. 2005 Feb;7(2):167-78. PMID:15710329 doi:10.1016/j.ccr.2005.01.008
  14. Huang L, Chen D, Liu D, Yin L, Kharbanda S, Kufe D. MUC1 oncoprotein blocks glycogen synthase kinase 3beta-mediated phosphorylation and degradation of beta-catenin. Cancer Res. 2005 Nov 15;65(22):10413-22. PMID:16288032 doi:65/22/10413
  15. Mukherjee P, Tinder TL, Basu GD, Gendler SJ. MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and normal T cells. J Leukoc Biol. 2005 Jan;77(1):90-9. Epub 2004 Oct 28. PMID:15513966 doi:jlb.0604333
  16. Lillehoj EP, Lu W, Kiser T, Goldblum SE, Kim KC. MUC1 inhibits cell proliferation by a beta-catenin-dependent mechanism. Biochim Biophys Acta. 2007 Jul;1773(7):1028-38. Epub 2007 Apr 22. PMID:17524503 doi:S0167-4889(07)00092-4
  17. Wei X, Xu H, Kufe D. Human mucin 1 oncoprotein represses transcription of the p53 tumor suppressor gene. Cancer Res. 2007 Feb 15;67(4):1853-8. PMID:17308127 doi:67/4/1853
  18. Pochampalli MR, el Bejjani RM, Schroeder JA. MUC1 is a novel regulator of ErbB1 receptor trafficking. Oncogene. 2007 Mar 15;26(12):1693-701. Epub 2006 Sep 18. PMID:16983337 doi:1209976

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