The role of p53 in malignancy

  • F. J. Keith
  • N. H. Russell
Part of the Cancer Treatment and Research book series (CTAR, volume 84)


Mutations in the p53 gene are currently the most common genetic lesion found in human cancers [1,2]. The p53 protein was initially discovered in coprecipitation studies with SV40 large T antigen [3], with which p53 forms a stable complex [4]. Initial studies linked mutations in p53 to malignant transformation and culture cell immortalization [5–7], and thus it was shown that the p53 gene was a tumor suppressor gene [8,9]. The p53 gene is expressed at low levels in normal cells of the body, with the highest levels being found in the testes, ovary, thymus, and spleen [10]. The levels of p53 protein rise due to an alteration in its half-life [11], in response to DNA damage by a variety of agents including irradiation, chemical carcinogens, and tumor viruses. The major function of these elevated levels of p53 protein is to prevent propogation of cells with damaged DNA and thus prevent the onset of cancer. It has been shown that wild-type p53 achieves this by causing G1 arrest of the cell cycle [12] and so allowing either repair of the damaged DNA or, in cases of high DNA damage, the onset of apoptosis [13]. Thus p53 acts as a ‘guardian of the genome’ [14] and is vital to maintenance of DNA integrity. It is therefore evident that mutations in such a crucial gene are disastrous for the cell, since further lesions in the genome are tolerated and the chance of malignant transformation increases [15].


Acute Lymphoblastic Leukemia Chronic Myeloid Leukemia Follicular Lymphoma Chronic Lymphatic Leukemia Hematopoetic Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Kluwer Academic Publishers, Boston 1996

Authors and Affiliations

  • F. J. Keith
  • N. H. Russell

There are no affiliations available

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