Insights into tumor suppressor protein p53 using three‐dimensional modeling and rapid prototyping technology

Abstract

Each year, nearly 40% of cancer patients in the U.S. die of the disease and more than 50% of tumors contain mutations of the TP53 gene encoding tumor suppressor protein p53. p53 functions in cell cycle control, senescence, and apoptosis in response to external stress. In normal cells, p53 binds the protein MDM2, promoting p53 degradation. Once activated by an environmental stress (DNA damage, oncogenes, or hypoxia), p53 releases MDM2, and, in turn, binds DNA. p53 induces the expression of p21, a protein that arrests cell division. p53 mutants are unable to activate p21, resulting in uncontrolled cell division and ultimately cancer.. Individuals with only one functional copy of TP53 will most likely develop Li‐Fraumeni Syndrome characterized by multiple tumor development in early adulthood. Pathogens such as human papillomavirus (HPV) can produce proteins that inactivate p53, leading to a higher incidence of cervical cancer. The Madison West High School SMART (Students Modeling a Research Topic) Team in collaboration with MSOE have built accurate three‐dimensional models of human p53 bound to DNA using 3D printing technology. By modeling p53, we hope to better understand how mutations in the protein lead to cancer as well as elucidating better mechanisms of cancer treatment. Supported by grants from the Howard Hughes Medical Institute, NIH‐NCRR‐SEPA and NIH T32 GM07215‐33.