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aBiochemistry Laboratory, IDI-IRCCS, Department of Experimental Medicine, University of Rome "Tor Vergata," Rome, Italy bMedical Research Council, Toxicology Unit, Leicester, UK
Address for correspondence: Gerry Melino, Medical Research Council, Toxicology Unit, Hodgking Building, Leicester University, Lancaster Road, P.O. Box 138, Leicester LE1 9HN, UK. gm89{at}le.ac.uk Ann. N.Y. Acad. Sci. 1010: 9-15 (2003).
Although p53 is clearly involved in the salvage pathway to DNA damage, its frequent mutations do not explain the efficacy of radiotherapy and chemotherapy. Indeed, around 50% of all human cancers show mutations in p53, and a further fraction show a functional inactivation of the protein. Nevertheless, patients seem to respond to therapy that would otherwise require a functional p53. At least in part, these responses could be explained by the pathway mediated by p73. This mechanism is parallel to, but independent of the p53 pathway. Several pieces of evidence show a significant interaction between these two proteins. Therefore, while p53 can be rightly defined as the guardian of the genome, we could think of p73 as the "assistant" guardian of the genome!
Key Words: apoptosis • cell death • DNA damage • cell cycle Abbreviations: TA-, full-length transactivating isoforms •
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N-, amino-terminal deleted isoforms, lacking the transactivation domain • TA, transactivation domain • DBD, DNA binding domain • OD, oligomerization domain • PR, proline-rich domain • SAM, sterile alpha motif • TI, trans-inhibitory domain • NES, nuclear exporting signal • SUMO, small ubiquitin-like modifier • PML, promyelocytic leukemia protein • SAPK, stress-activated protein kinases • JNK, Jun kinase