8p6i

Structural highlights

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

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]}

References

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