1. FBW7/CDC4 and Endometrial Cancer Michael Mastropole

2. Overview FBW7/CDC4 is a family of genes Tumor suppressor Directly binds to cyclin E Mutated in about 16% of endometrial cancers

3. Ubiquitylation http://upload.wikimedia.org/wikipedia/commons/7/7f/Ubiquitylation.png

4. The SCF Complex (E3 ligase) Wang et al. 2012

5. CDC4 targets Cyclin E for Proteolysis Strohmaier et al. 2001

6. http://eweb.furman.edu/~wworthen/bio111/4cyclins.jpg Cyclin E is required for G1/S Transition

7. Mouse Model Wang et al. 2012

8. Endometrial Cancer Endometrium- lining of the uterus Typically occurs within a few decades of menopause 49,560 new cases in 2013

9. hCDC4 mutations Spruck et al. 2002

10. Treatments Surgery – Hysterectomy along with removal of ovaries, fallopian tubes, and lymph nodes – Helps stage the cancer Chemotherapy – Taxol Radiation Potential Treatments – Cdk2 inhibitors www.cancer.org

11. Prognosis 1 year survival rate – 92% 5 year survival rate if cancer has not spread – 95% 5 year survival rate if cancer has spread – 23% www.nlm.nih.gov

12. References http://www.nature.com/nature/journal/v413/n6 853/full/413316a0.html http://cancerres.aacrjournals.org/content/62/16/ 4535.long http://www.cancer.org/cancer/endometrialcance r/detailedguide/endometrial-uterine-cancer- treating-by-stage http://www.nlm.nih.gov/medlineplus/ency/articl e/000910.htm http://www.sciencedirect.com/science/article/pii /S0014579312002049