An Introduction to the Structure, Regulation, and Transcriptional Activity of
the Tumor Suppressor Protein p53
Dr. Eyal Arbely, Department of Chemistry, Ben-Gurion University of the Negev
Date and Time: April 30, 2018, 15:00
Location: Location: Prof. Wilhelmina Cohen Auditorium in the Pediatric Division at Soroka Medical Center
Refreshments will be served 15 minutes before the lecture
The p53 protein, encoded by the TP53 gene, is involved in the regulation and execution of numerous cellular processes via different modes of action. The classic and probably most studied activity of p53 is its role as a transcription factor. p53 is a sequence-specific DNA binding protein that regulates the transcription of an array of genes. In response to various stress signals (e.g., DNA damage), p53 is activated and orchestrates a complex mechanism that determines cell fate. For example, p53 can promote cell cycle arrest in order to allow DNA repair, or in cases of severe DNA damage it can promote cell death by activating pro-apoptotic cell responses. This role may explain why p53 is referred to as 'the guardian of the genome' and why mutations in TP53 (found in over 50% of human cancers) are often linked to poor prognosis. Moreover, TP53 mutations are a hallmark of hereditary cancer predisposition disorder known as Li-Fraumeni syndrome.
Our understanding of the complex p53 network has improved dramatically since the protein was discovered. However, an increasing number of new roles for p53 have recently been reported and despite intensive efforts, many aspects of p53's cellular activities are still an enigma, and p53 remains a highly dynamic and rapidly expanding area of study. In my talk, I will provide a general, yet broad, review on our current understanding of the various roles of p53, its regulation, as well as its structure.
p53, Guardian of the Genome: Insights, Promises and Challenges
Prof. Moshe Oren, Department of Molecular Cell Biology, Weizmann Institute of Science
Date and Time: May 1, 2018, 8:00
Location: Prof. Wilhelmina Cohen Auditorium in the Pediatric Division at Soroka Medical Center
Breakfast served 30 minutes before the lecture
The TP53 gene, coding for the p53 tumor suppressor protein, is the most frequently mutated gene in human cancer: about 50% of all cancer cases carry TP53 mutations. The p53 protein serves as a major barrier against cancer, by maintaining genome stability and cellular homeostasis and by eliminating potential cancer cells from the replicative pool. In the majority of tumors that harbor TP53 mutations, high amounts of the mutant p53 protein accumulate in the cancer cells. This may contribute to cancer progression not only by removing p53's tumor suppressor functions, but also by endowing the mutant p53 protein with new oncogenic functions. Furthermore, in many of the tumors that retain non-mutated (“wild-type") p53, the functionality of the p53 protein is compromised by other genetic or epigenetic alterations.
On the basis of this knowledge, a variety of attempts are being made to develop novel therapeutic strategies for restoring p53 functionality in cancer cells. Although pre-clinical studies and early phase clinical trials have shown great promise, severe side effects have been observed and none of those compounds has so far gained approval.
The lecture will discuss the basic biology and biochemistry of p53, and the current status of the therapeutic approaches that are being explored.