Melino Gerry
Biochemistry Laboratory, IDI-IRCCS, Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
Ann N Y Acad Sci. 2003 Dec;1010:9-15. doi: 10.1196/annals.1299.002.
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!
尽管p53显然参与了DNA损伤的补救途径,但其频繁突变并不能解释放疗和化疗的疗效。实际上,在所有人类癌症中,约50%显示p53突变,另有一部分显示该蛋白功能失活。然而,患者似乎对原本需要功能性p53的治疗有反应。这些反应至少部分可以由p73介导的途径来解释。这种机制与p53途径平行,但独立于p53途径。多项证据表明这两种蛋白之间存在显著相互作用。因此,虽然p53可以被恰当地定义为基因组守护者,但我们可以将p73视为基因组的“辅助”守护者!