Adenomatous polyposis coli
From Proteopedia
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'''<scene name='84/843011/Pokus1/1'>Adenomatous polyposis coli (APC)</scene>''' is a multidomain tumour suppressor protein involved in the regulation of various cellular processes, such as cell adhesion, migration or proliferation<ref name="Zhang2017">Zhang, L. and Shay, J. W. (2017) ‘Multiple Roles of APC and its Therapeutic Implications in Colorectal Cancer.’, Journal of the National Cancer Institute, 109(8). doi: 10.1093/jnci/djw332.</ref>. It is expressed in plethora of organs and tissues, e. g. cerebral cortex, bronchi or the gastrointestinal tract<ref name="proteinatlas">https://www.proteinatlas.org/ENSG00000134982-APC/tissue</ref>. Germline truncation mutations of APC result in familial adenomatous polyposis, a hereditary form of colon cancer<ref name="Ficari2000">Ficari, F. et al. (2000) ‘APC gene mutations and colorectal adenomatosis in familial adenomatous polyposis’, British Journal of Cancer. Churchill Livingstone, 82(2), pp. 348–353. doi: 10.1054/bjoc.1999.0925.</ref>. Additionally, loss of the C-terminal portion of APC is detected in about 80 % of sporadic colon cancers<ref name="Rowan2000">Rowan, A. J. et al. (2000) ‘APC mutations in sporadic colorectal tumors: A mutational “hotspot” and interdependence of the “two hits”’, Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 97(7), pp. 3352–3357. doi: 10.1073/pnas.97.7.3352.</ref>. | '''<scene name='84/843011/Pokus1/1'>Adenomatous polyposis coli (APC)</scene>''' is a multidomain tumour suppressor protein involved in the regulation of various cellular processes, such as cell adhesion, migration or proliferation<ref name="Zhang2017">Zhang, L. and Shay, J. W. (2017) ‘Multiple Roles of APC and its Therapeutic Implications in Colorectal Cancer.’, Journal of the National Cancer Institute, 109(8). doi: 10.1093/jnci/djw332.</ref>. It is expressed in plethora of organs and tissues, e. g. cerebral cortex, bronchi or the gastrointestinal tract<ref name="proteinatlas">https://www.proteinatlas.org/ENSG00000134982-APC/tissue</ref>. Germline truncation mutations of APC result in familial adenomatous polyposis, a hereditary form of colon cancer<ref name="Ficari2000">Ficari, F. et al. (2000) ‘APC gene mutations and colorectal adenomatosis in familial adenomatous polyposis’, British Journal of Cancer. Churchill Livingstone, 82(2), pp. 348–353. doi: 10.1054/bjoc.1999.0925.</ref>. Additionally, loss of the C-terminal portion of APC is detected in about 80 % of sporadic colon cancers<ref name="Rowan2000">Rowan, A. J. et al. (2000) ‘APC mutations in sporadic colorectal tumors: A mutational “hotspot” and interdependence of the “two hits”’, Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 97(7), pp. 3352–3357. doi: 10.1073/pnas.97.7.3352.</ref>. | ||
| - | == | + | == The overall structure of APC == |
| + | The APC protein, its primary sequence encompassing 2843 aminoacids<ref name="uniprot">https://www.uniprot.org/uniprot/P25054</ref>), consists of multiple domains, which enable it to interact with diverse partners. At the N-terminus, an oligomerisation domain is found, enabling the APC protein to oligomerise. It is followed by seven so called armadillo repeats, which form a groove for binding of a guanine nucleotide exchange factor Asef<ref name="Zhang2012">Zhang, Z. et al. (2012) ‘Structural basis for the recognition of Asef by adenomatous polyposis coli’, Cell Research. Nature Publishing Group, 22(2), pp. 372–386. doi: 10.1038/cr.2011.119.</ref>. The central part of APC contains three 15 aminoacid long repeats followed by seven 20 aminoacid long repeats<ref name="Zhang2017"/>. These motifs serve as binding sites for β-catenin<ref name="Hou2011">Hou, F. et al. (2011) ‘MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response.’, Cell. Elsevier, 146(3), pp. 448–61. doi: 10.1016/j.cell.2011.06.041.</ref>. In between the 20 aminoacid repeats, three SAMP regions are dispersed, enabling the interaction with Axin<ref name="Zhang2017"/>. At the C-terminus, a basic domain responsible for binding to microtubules as well as EB1 interaction domain are present<ref name="Su1995">Su, L. K. et al. (1995) ‘APC Binds to the Novel Protein EB’, Cancer Research, 55(14), pp. 2972–2977.</ref><ref name="Zhang2017"/>. | ||
| + | Interestingly, majority of somatic mutations occurs in so called mutation cluster region (MCR) between codons 1286 and 1513 <ref name="Miyoshi1992">Miyoshi, Y. et al. (1992) Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene | Human Molecular Genetics | Oxford Academic, Human Molecular Genetics, Vol. 1, No. 4 229-233. Available at: https://academic.oup.com/hmg/article/1/4/229/730109 (Accessed: 22 April 2020).)</ref>. | ||
| + | [[Image:APC.png]] | ||
== Disease == | == Disease == | ||
Revision as of 20:25, 28 April 2020
Adenomatous polyposis coli
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References
- ↑ 1.0 1.1 1.2 1.3 Zhang, L. and Shay, J. W. (2017) ‘Multiple Roles of APC and its Therapeutic Implications in Colorectal Cancer.’, Journal of the National Cancer Institute, 109(8). doi: 10.1093/jnci/djw332.
- ↑ https://www.proteinatlas.org/ENSG00000134982-APC/tissue
- ↑ Ficari, F. et al. (2000) ‘APC gene mutations and colorectal adenomatosis in familial adenomatous polyposis’, British Journal of Cancer. Churchill Livingstone, 82(2), pp. 348–353. doi: 10.1054/bjoc.1999.0925.
- ↑ Rowan, A. J. et al. (2000) ‘APC mutations in sporadic colorectal tumors: A mutational “hotspot” and interdependence of the “two hits”’, Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 97(7), pp. 3352–3357. doi: 10.1073/pnas.97.7.3352.
- ↑ https://www.uniprot.org/uniprot/P25054
- ↑ Zhang, Z. et al. (2012) ‘Structural basis for the recognition of Asef by adenomatous polyposis coli’, Cell Research. Nature Publishing Group, 22(2), pp. 372–386. doi: 10.1038/cr.2011.119.
- ↑ Hou, F. et al. (2011) ‘MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response.’, Cell. Elsevier, 146(3), pp. 448–61. doi: 10.1016/j.cell.2011.06.041.
- ↑ Su, L. K. et al. (1995) ‘APC Binds to the Novel Protein EB’, Cancer Research, 55(14), pp. 2972–2977.
- ↑ Miyoshi, Y. et al. (1992) Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene | Human Molecular Genetics | Oxford Academic, Human Molecular Genetics, Vol. 1, No. 4 229-233. Available at: https://academic.oup.com/hmg/article/1/4/229/730109 (Accessed: 22 April 2020).)
