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Cancer and LKB1 By: Rosanna Chan, Ria Shome, Chloe Ortbals, Alex Maynard, Michelle Reznikova
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What is Cancer? DNA malignant and benign cancer Current research
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What is a Tumor Suppressor? Anti-oncogene Checkpoints Checking energy homeostasis
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Energy Homeostasis aka. Metabolic Stress ATP & AMP Anabolic pathways –ATP + small molecules => AMP + large molecule Catabolic pathways –AMP + large molecule => ATP + smaller molecules
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AMPK Facts Protein kinase Metabolic stress (anabolic & catabolic)
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How is LKB1 a Tumor Suppressor? -LKB1 and AMPK –energy homeostasis (AMP:ATP ) -prevents cell from dividing if there is an imbalance –Cancerous cells If LKB1 is absent the cell divides more often (Peutz Jeghers Syndrome)
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Molecular Structure of LKB1 Arg74= reduce catalytic activity -arginine RESIDUES MUTATED IN PJS Interaction with STRAD –CFT [311-347]= reduced catalytic activity –c-terminal flanking tail Asp208 Arg74 Thr230 Glu199 Ser232
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LKB1-STRAD-MO25 Complex Function
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STRAD Molecular Structure - pseudokinase that helps activate LKB1 Leu241 Gln251 Gln286
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MO25 Molecular Structure scaffolding protein o Orients the activation loop of LKB1 Phe243 Arg240
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How Does LKB1 Affect Us? where it is expressed PJS/Cancer
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To Conclude LKB1
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Citations "Adenosine Monophosphate." ChemSpider. N.p., n.d. Web. 06 Dec. 2013.. "Case Study: Thermodynamics of ATP." Chemwiki. N.p., n.d. Web. 06 Dec. 2013.. Cell Cycle with Checkpoints. Digital image. N.p., n.d. Web. 5 Dec. 2013.. Hardie, D. Grahame, and Dario Alessi. "LKB1 and AMPK and the cancer-metabolism link - ten years after." BMC Biology. N.p., n.d. Web. 4 Dec. 2013.. Stick Figure. Digital image. Portablestudios. N.p., n.d. Web.. Serine/threonine Kinase 11. Digital image. Wikipedia. N.p., n.d. Web. Van Aalten, Daan, and Elton Zeqiraj. "Structure of the LKB1-STRAD-MO25 Complex Reveals an Allosteric Mechanism of Kinase Activation." ScienceMag. N.p., 5 Nov. 2009. Web.. "What Is Cancer?" What Is Cancer? N.p., n.d. Web. 04 Dec. 2013..
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