Tumor suppressor gene p53: how the guardian of our genome prevents cancer

Lectures: 1 session / week, 2 hours / session

At least one of the following courses:

7.03 Genetics

7.05 General Biochemistry

7.06 Cell Biology

7.08 Biological Chemistry II

Cancer is a leading cause of death worldwide. Cancer involves uncontrolled cell growth, resistance to cell death, failure to differentiate into a particular cell type and increased cellular motility. A family of gate-keeper genes, known as tumor suppressor genes, plays important roles in preventing the initiation and progression of cancer. Among these, p53 is the most famous. More than 50% of human cancers harbor mutations in or deletion of p53. p53 is induced by upstream signals, such as DNA damage and hyperactive cell-growth signals. The p53 protein, functioning as a transcription factor, binds to the promoters of many target genes involved in the cell cycle, programmed cell death (apoptosis) and DNA repair. Because of its essential role in maintaining genomic integrity, p53 is often called the guardian of the genome.

During this course, we will study how p53 serves as a pivotal tumor suppressor gene in preventing cancer. We will examine the discovery of the p53 protein, the spectrum of p53 mutations in human cancer and the role of p53 as a transcription factor. In addition, we will discuss the function of p53 in DNA damage, cell death, cell cycle regulation, and genome integrity. We will also consider some recent studies of p53 mutant mouse models and the regulation by p53 of small RNA expression. Finally, we will discuss how future cancer treatments might be achieved by therapies that restore p53 function to tumor cells.

The objectives of this course are:

The content of this course will be based on the primary research literature. For each class, students will be assigned to read two papers and formulate two questions per paper prior to each class. Questions might pertain to background, interpretation of results, a technique, follow-up experiments, etc. During class we will discuss the papers interactively as a group. Students might be asked to discuss specific figures or tables to answer questions about the papers. At the end of each session, the instructor will introduce the papers for the next week.

This course is graded pass/fail. Grading will depend on student attendance, participation in class discussions and completion of two assignments.

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