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Smad4 (Dpc4) in Colon Cancer. Elizabeth Jarvis March 22, 2007. Objectives:. I. Cell Biological Role of Smad4 II. Biological Role of Protein (What does it do for the Organism?) III. Connection to Cancer Colon and Pancreatic. I. Cell Biological Role of Smad4. Smads.
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Smad4 (Dpc4) in Colon Cancer Elizabeth Jarvis March 22, 2007
Objectives: • I. Cell Biological Role of Smad4 • II. Biological Role of Protein (What does it do for the Organism?) • III. Connection to Cancer • Colon and Pancreatic
Smads • Transcription Regulators • Different Classes- • Smad2 and 3: Phosphorylated at carboxyl-terminal serines • Smad4: co-Smad
Cellular Machinery • TGF-β = Serine/Threonine Kinase • Smad4 is NOT phosphorylated Fazhi Li, M.D. et al. (2005). World J. Surg. 29, 306-311.
How was this cell biological role determined? • Presence of Smad in MC-26 cell line→ Functioning TGF-β signaling pathway Fazhi Li, M.D. et al. (2005). World J. Surg. 29, 306-311.
How was this cell biological role determined? • Dominant Negative forms of Smads block TGF-β signaling Fazhi Li, M.D. et al. (2005). World J. Surg. 29, 306-311.
TGF/BMP Molecules Signal Through the SMADs Jonas Larsson and Stefan Karlsson. (2005). Oncogene.24, 5676−5692.
II. Biological Role of Protein What does it do for the Organism?
Disruption by Homologous Recombination • Embryonic lethal by day 7.5 • Defective mesoderm and visceral endoderm development in Smad4 mutant embryos Christian Sirard et al. (1998). Genes and Development. 12, 107-119.
Smad4 Gastrulation Defect • The gastrulation defect in Smad4 mutant embryos results from a defective visceral endoderm Christian Sirard et al. (1998). Genes and Development. 12, 107-119.
III. Connection to Cancer Colon and Pancreatic Cancer
Smad4 mutation in the progression of colorectal carcinogenesis Michiko Miyaki and Toshio Kuroki. (2003). Biochem and Biophysical Res. Comm. 306, 799-804.
Somatic mutations of the Smad4 gene detected in human cancer • Majority of Smad4 gene mutations in human cancer are missense, nonsense, and frameshift mutations at MH2 Michiko Miyaki and Toshio Kuroki. (2003). Biochem and Biophysical Res. Comm. 306, 799-804.