| Popis: |
The p53 tumor suppressor protein is critical in the control of cell growth and the maintenance of genomic stability. These activities are due, at least in part, to its ability to form homooligomers that bind to specific DNA sequences and activate transcription. Recently discovered, p73, a homologue of p53 binds to canonical p53 DNA-binding sites in vitro and can, at least when overproduced, transcriptionally activate p53 target genes in vivo. The p73 gene is rarely mutated but frequently overexpressed in human tumors. p73 generates transactivating forms (TAp73) as well as a number of N-terminally truncated transactivation-deficient transdominant isoforms (called deltaTAp73). Recently was discovered that p53, like p73, has a second promoter P2 and undergoes alternative splicing to generate multiple isforms. One deltaNp53 isoform is transcribed from P2 (called delta133p53, lacking transactivation domain) and another (called delta40p53) produced from first promoter, but has other initiation site then wild type p53, might play important roles in carcinogenesis. Defining the interactions between p53/p73 is necessary to gain insight into how the p53 isoforms modulate the functions of p73. Although mutational p53 status has been an important factor for predicting prognosis and guiding therapy, the discovery of inhibitory p53/p73 network could have a major clinical impact in prognostic use and p53 targeted drug design. |
