Contribution of p53, p63, and p73 to the developmental diseases and cancer.
Tumor suppressor TP53 gene is one of the most mutated genes in human genome. Inactivating somatic mutations and disruption of p53 protein have been described in almost all human malignancies. Its inactivation by germline mutation leads to the rare but severe familial precancerosis termed Li-Fraumeni syndrome. This syndrome is characterized by the early onset of different types of cancers including soft-tissue sarcomas, breast and brain cancers, leukemias, lung, laryngeal cancers, and adrenocortical carcinomas. The key role of p53 in tumor suppression has been confirmed in animal models as well. The p53 -knock-out and knock-in animals were born alive but were tumor prone. In the late nineties, two genes with high homology with TP53 were discovered, TP73 and TP63, respectively. Animal models showed that p73 is an important player in neurogenesis, sensory pathways and homeostatic control. The p63 is critical for the development of stratified epithelial tissues such as epidermis, breast, and prostate. Despite the structural similarities with p53, the function of these proteins in tumorigenesis is controversial. On one hand, there are evidences that both, p63 and p73-deficient animals are not tumor prone; on the other hand, there is evidence that such animals develop tumors later during their life. Unlike in TP53 gene, mutations in TP63 and TP73 genes are rare, however, germline mutations in TP63 are linked to the human developmental diseases. In this minireview, we describe the contribution of the p53, p63, and p73 to human pathology with emphasis on their different roles in development and tumorigenesis.
Tomkova
K
K
Laboratory of Cancer Genetics, Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, Bratislava, Slovakia. exonktom@savba.sk
Tomka
M
M
Zajac
V
V
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D047108:Embryonic Development; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins