The tumour suppressor protein p53 is one of the best characterized proteins in the cell, in part, because the gene encoding it (TP53) is mutated in nearly 50% of all human tumors. For years, p53 was believed to be in a class of its own. The discovery of p63 and p73, which closely resemble p53, raised the possibility that they, too, might be involved in suppressing the formation of tumours. But numerous investigations of p73 failed to unearth mutation of its gene (TP73) in cancers. Overexpression of TP73, can, however, trigger programmed cell death (known as apoptosis)—in a similar manner to overexpression of TP53, leading some to speculate that perhaps some of the functions previously ascribed to p53 are in fact carried out by p73 in normal cells.
Thorsten Stieve and Birgitte Putzer (University of Essen Medical School in Essen, Germany) now present data that support this hypothesis (Nature Genetics, Vol. 26, Issue 4, 01 Dec 2000). They focused on E2F1, a protein that is known to regulate p53 levels and is also known to have two mutually antagonistic roles. When overexpressed, it can lead to tumour formation, but at normal levels, it mediates cell death. Stieve and Putzer wondered whether E2F1 also regulates levels of p73. They found that indeed, it does—and that through ramping up levels of p73, E2F1 can instigate apoptosis. Furthermore, E2F1 can trigger p73 cell death in the absence of p53. The elucidation of this cell-death pathway, this study, together with two studies recently published in Nature, has implications for the treatment of cancers—especially those that carry TP53 mutations.
Dr. Brigitte Putzer
University of Essen
Telephone: +49 201 723 3158/3153
Fax: +49 201 723 5974
(News & Views)
Dr. Scott Lowe
Cold Spring Harbor Laboratory
Cold Spring Harbor, New York
Telephone: +1 516 367 8406
Fax: +1 516 367 8454
(C) Nature Genetics press release.
Message posted by: Trevor M. D'Souza
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