Cancer and LKB1

By: Rosanna Chan, Ria Shome, Chloe Ortbals, Alex Maynard,

Michelle Reznikova

What is Cancer?

• DNA• malignant and benign cancer• Current research

What is a Tumor Suppressor?

• Anti-oncogene• Checkpoints• Checking

energy homeostasis

Energy Homeostasisaka. Metabolic Stress

• ATP & AMP• Anabolic pathways– ATP + small molecules => AMP + large

molecule

• Catabolic pathways– AMP + large molecule => ATP + smaller

molecules

AMPK Facts• Protein kinase• Metabolic stress (anabolic & catabolic)

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)

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

LKB1-STRAD-MO25 Complex Function

STRAD Molecular Structure

• - pseudokinase that helps activate LKB1

Leu241

Gln251

Gln286

MO25 Molecular Structure• scaffolding

proteino Orients the

activation loop of LKB1

Phe243

Arg240

How Does LKB1 Affect Us?

• where it is expressed• PJS/Cancer

To Conclude LKB1

Citations• "Adenosine Monophosphate." ChemSpider. N.p., n.d. Web. 06 Dec. 2013.

<http://www.chemspider.com/Chemical-Structure.5858.html>.• "Case Study: Thermodynamics of ATP." Chemwiki. N.p., n.d. Web. 06 Dec. 2013.

<http://chemwiki.ucdavis.edu/Physical_Chemistry/Thermodynamics/Case_Studies/Case_Study:_Thermodynamics_of_ATP>.

• Cell Cycle with Checkpoints. Digital image. N.p., n.d. Web. 5 Dec. 2013. <http://answers.tutorvista.com/145710/what-is-the-cell-cycle.html>.

• 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. <http://www.biomedcentral.com/1741-7007/11/36>.

• Stick Figure. Digital image. Portablestudios. N.p., n.d. Web. <http://portablestudios.com.au/?attachment_id=75#>.

• 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. <http://www.sciencemag.org/content/326/5960/1707.full>.

• "What Is Cancer?" What Is Cancer? N.p., n.d. Web. 04 Dec. 2013. <http://www.cancer.org/cancer/cancerbasics/what-is-cancer>.