Our paper entitled: "p53: 25 years after its discovery" provides a concise overview of p53. It follows the history of p53 from the time of its discovery in 1979 to the present, highlights its key functions, overviews its role in cancer chemoprevention and treatment, and provides a detailed list of relevant p53-related websites. In 1992, Sir David P. Lane accurately described p53 as the "guardian of the genome." "p53" appears in the title of over 16,000 scientific articles on a PubMed search. The high interest in p53 is largely due to the fact that it is the most frequently altered protein in human cancer and that it is at the crossroads of cellular stress responses. The concise nature of "p53: 25 years after its discovery" is a target of citation for scientists interested in the broad field of cellular stress responses to those interested in p53 and its (many) interacting proteins and signaling pathways.

As mentioned, p53 was discovered over a quarter century ago. However, there is an ever-growing list of p53 interacting proteins, p53 family members, p53 functions, and stress factors that activate p53. This list is useful to others in the field, and is reviewed in a concise manner in our article.

p53 is one of the most protective anti-cancer proteins in our body. If it is not there, or if it is somehow mutated, cells in our body grow uncontrollably (a definition of cancer).

How does p53 protect us from cancer?

It guards our genome, and thus, has been coined "guardian of the genome." It plays a role in stopping cells from dividing to allow for DNA repair to occur once it is damaged, it plays a role in driving damaged cells to die—and therefore, the cells won’t hang around in our body and have a chance to become cancerous—and it drives the repair of damaged DNA. Imagine if you were suddenly exposed to radiation, p53 would sense this exposure, and rise up to defend against all the harmful effects of radiation on your body (such as genetic damage). If p53 did not do its job, the cells damaged by the radiation would become cancerous in time (months to years). This is why we are actively seeking ways to activate p53 during conventional cancer treatment, or seeking ways to add p53 to our bodies in more novel treatment strategies.

Dr. Curtis C. Harris has been the Chief of the Laboratory of Human Carcinogenesis at the National Cancer Institute (NCI) in Bethesda, Maryland, for as many years as p53 has been known to exist. He pioneered the development of in vitro models using human tissues and cells to compare metabolic pathways for the activation of chemical carcinogens and detoxification in humans and laboratory animals. He and Andres Klein-Szanto were the first to show that chemical carcinogens in tobacco smoke induce neoplastic transformation of human bronchial epithelial cells in the laboratory. He has gained international recognition for his cellular and molecular studies of asbestos-induced human pleural mesothelioma and lung cancer. Dr. Harris burst into the p53 field in the early 1990s with high-impact papers identifying p53 mutational hotspots in human cancers, identifying p53 as one of the most common genetic lesions in human cancers, and "outing" p53 as a tumor suppressor gene. Since then, he has published many papers in the field. With Drs. Stefan Ambs and Kathy Forrester, Dr. Harris provided evidence of an interaction between nitric oxide and p53.

Dr. Perwez Hussain extended these observations by generating data indicating p53 is mutated in many chronic inflammatory diseases (diseases in which nitric oxide is produced in high quantities). Dr. Hussain continues these studies at the Laboratory of Human Carcinogenesis.

In 1999, Dr. Lorne Hofseth joined the Laboratory of Human Carcinogenesis, where he was encouraged to build upon the role of p53 as a molecular node involved in inflammatory-driven carcinogenesis. He now holds a tenure-track appointment at the University of South Carolina where he continues to study the molecular mechanisms linking chronic inflammation to cancer.

p53 is a target of many chemoprevention and cancer treatment strategies. Given its wide range of functions, and its growing role in diseases other than cancer (e.g., chronic inflammation and aging), targeting p53 may lead to a better and longer life-span for many individuals.