| Product description |
Mouse monoclonal [608 - 45] to PAG608Human cancer is a multistep process in which accumulation of genetic damage occurs to key regulatory genes, known as oncogenes, and to tumorsuppressor genes. The wild-type (wt) p53 gene is classified as a tumor-suppressor gene (Levine et al). Point mutations in the wild-type gene has been suggested as a key event in the development of malignancy, since the mutant protein actually acts as a dominant oncogene. Indeed, mutations of the p53 gene are the most common molecular changes identified in human cancer; they have been reported to be a frequent feature of breast, lung, colon, ovarian, brain, testicular and bladder cancers, melanoma, neurofibrosarcoma and certain types of leukemia (Midgley et al). In all these cases, mutations are found only in the tumor tissue and not in the normal tissue. A major outcome of such mutations is inactivation of the biochemical and biological functions of the wt p53 protein (Bates et al). Among the biological effects elicited by wt p53, the most documented are cell cycle arrest, apoptosis and its ability to act as a transcriptional regulator. p53 is a transcription factor capable of binding in a sequence-specific manner to well defined DNA elements and inducing the transcription of genes residing in the vicinity of such p53 response elements (Israeli et al). Also, p53 can repress the transcription of many genes, although direct sequence specific interactions between p53 and these genes are generally not involved in this process. Sequence specific transactivation (SST) can either be obligatory or dispensable for apoptosis. Though, it is most likely that an optimal apoptotic effect of p53 requires a combination of both SST and other SST-independent biochemical activities. Among the target genes whose sequence-specific transactivation by wt p53 may promote apoptosis are: bax, the gene coding IGF-BP3, the mammalian homologue of the Drosophila seven in absentia gene, and PAG608. PAG608, a novel p53 target gene, encodes a nuclear zinc finger protein whose overexpression promotes apoptosis in transfected human tumor-derived cells. PAG608 exhibits a predominantly nuclear localization. The staining pattern of the transfected protein suggests that it is localized preferentially to nucleoli. This is compatible with a possible role in regulation of rRNA synthesis by mediating a particular inhibitory effects through interference with optimal production of new ribosomes. The conspicuous induction of PAG608 in cells undergoing p53-dependent apoptosis and its ability to promote apoptosis in transiently transfected cells, raises the possibility that it plays some role in facilitating the apoptotic activities of p53. Monoclonal antibodies reacting specifically with PAG608 may be applied in diverse cellular and molecular approaches for the study of nuclear processes and to elucidate the nature of the involvement and activity of zinc finger proteins. |
