1. p57, Tumorigenesis, and Beckwith-Wiedemann Syndrome Ashley Albright

2. p57 is a member of the Cip/Kip family of CKIs Encoded by CDKN1C Cyclin/CDK binding domain PAPA Repeat QT domain

3. The ability of p57 to inhibit Cyclin/CDK suggests it is a tumor suppressor, however p57 levels are high in some cancers

4. p57 inhibits proliferation by binding and inhibiting CDKs G1-S and G2-M transition Disruption of CDK/cyclin or PCNA binding region reduces ability of p57 to inhibit proliferation

5. p57 can suppress or promote apoptosis However, other data suggests p57 suppresses pro-apoptotic factors at cell cycle checkpoints

6. p57 and other Cip/Kip proteins promote cellular migration which leads to tumor metastasis

7. p57 homozygous mutants cannot exit the cell cycle, allowing cells to become over-proliferative

8. p57 misregulation can lead to cancer via many pathways DNA methylation and Histone Modifications MicroRNAs Post- translational Modification

9. CDKN1C has been implicated in Beckwith-Wiedemann Syndrome 1 in 12,000 newborns Primarily due to improper imprinting Classified as an overgrowth syndrome Susceptible to tumors

11. BWS patients have a higher risk of developing abnormal tissue growth

12. References "Beckwith-Wiedemann Syndrome." Genetics Home Reference. Accessed March 30, 2015. http://ghr.nlm.nih.gov/condition/beckwith-wiedemann-syndrome. Bilodeau, S., et al. "Distinct Developmental Roles of Cell Cycle Inhibitors P57Kip2 and P27Kip1 Distinguish Pituitary Progenitor Cell Cycle Exit from Cell Cycle Reentry of Differentiated Cells." Molecular and Cellular Biology 29, no. 7 (2009): 1895-908. Cooper, W., et al. "Molecular Subtypes and Phenotypic Expression of Beckwith– Wiedemann Syndrome." European Journal of Human Genetics 13 (2005): 1025- 032 Denicourt, C., et al. "Cip/Kip Proteins: More than Just CDKs Inhibitors." Genes & Development 18 (2004): 851-55. Hatada, I., et al."An Imprinted Gene P57KIP2 Is Mutated in Beckwith–Wiedemann Syndrome." Nature Genetics 14 (1996): 171-73. Yan, Y., et al. "Ablation of the CDK Inhibitor P57 Kip2 Results in Increased Apoptosis and Delayed Differentiation during Mouse Development." Genes & Development 11 (1997): 973-83.