BMPR1A Bone Morphogenetic Protein Receptor 1 A (Juvenile Polyposis & Colon Cancer) Hallie Wieters.
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Transcript of BMPR1A Bone Morphogenetic Protein Receptor 1 A (Juvenile Polyposis & Colon Cancer) Hallie Wieters.
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BMPR1ABone Morphogenetic Protein Receptor 1 A
(Juvenile Polyposis & Colon Cancer)
Hallie Wieters
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BMPR1A is part of a TGF-βReceptor Serine/Threonine Kinase
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There are multiple ligands, receptors and many
SMADs
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BMPs can regulate cell differentiation, growth inhibition
or apoptosis
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KO BMPR1-A mutant mouse
leads to embryonic lethality due to
failed gastrulation
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Continual loss of intestinal cells and repetitive cell cycle entry causes the
colon to be prone to mutations
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Juvenile Polyposis leads to colon polyp formation and thus a predisposition to
colon cancer
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Juvenile Polyposis is caused by germline mutations and loss of heterozygosity at BMPR1-A loci
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Mutated BMPR1-A leads to increased proliferation, decreased
differentiation, increased number of stem cells and cell persistence
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Scientists have created a mouse model of juvenile polyposis by
mutating BMPR1-A
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Juvenile Polyposis can be diagnosed through genetic screening and treated
through colon surveillance
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SummaryBMPR1A is a threonine/serine kinase receptor in the
TGF-βfamily (growth-inhibitorytumor suppressor)
Germline Mutations cause a nonfunctional receptor leading to propagation of proliferating signals and an increase stem cells
Inherited autosomal dominantly recessive at the cellular level
Lack of regulation in proliferation leads to development of polyps in the colon Juvenile Polyposis
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ReferencesHe, X. C., Zhang, J., Tong, W.-G., Tawfik, O., Ross, J., Scoville, D. H., Tian, Q., Zeng, X., He, X., Wiedemann, L. M., Mishina, Y., Li, L. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nature Genet. 36: 1117-1121, 2004.Cichy, Wojciech, Beata Klincewicz, and Andrzej Plawski. “Juvenile Polyposis Syndrome.” Archives of
Medical Science : AMS 10.3 (2014): 570–577. PMC. Web. 2 Mar. 2015.Mishina, Yuji,Suzuki, A., Ueno, N., Behringer, R. Bmpr encodes a type 1 bone morphogenetic protein
receptor that is essentail for gastrulation during mouse embryogenesis. Genes & Development, 9
(1995): 3027-3037. Waite, Kristen, Eng, C., From developmental disorder to heritable cancer : It’s all in the TGF-B
Family. Nature Reviews: Genetics. 4 (2003) : 763-772.
Zhou, Xiao-Ping et al. “Germline Mutations in BMPR1A/ALK3 Cause a Subset of Cases of Juvenile Polyposis Syndrome and of Cowden and Bannayan-Riley-Ruvalcaba Syndromes.” American Journal of Human Genetics 69.4 (2001): 704–711. Print.
Chen, Di, Mundy, G. “Bone Morphogenetic Proteins”. Growth Factors 22 (2004):233-241