| Description |
Gene therapy is currently used not only to correct the cellular errors associated with tumorigenesis, but to also provide enhanced cellular functions against tumor development. Over half of all known cancers have either a loss of function or inactive tumor suppressor p53. In response to various stress or oncogenic signals, the tumor suppressor protein p53 mediates cellular response via induction or repression of certain genes. Tumor suppressor p53 functions mainly as a transcription factor controlling genes involved in DNA repair, senescence, cell cycle arrest, and most importantly, apoptosis. Accumulation of p53 in the nucleus is necessary for its transcriptional activities; however, inactivation of the transcriptional activity of p53 has been shown to be associated with tumor formation. Correspondingly, loss of structural stability and thermodynamically destabilized p53 mutants are also associated with tumorigenesis. We have analyzed the literature on the stability and function of p53. Several research groups focus on thermodynamically stabilized p53, whereas others primarily targeted the restoration and enhancement of the transcriptional activity of p53. Here, we use a holistic approach by combining both concepts. We have successfully constructed plasmids extracted from literature, including the thermodynamically stabilized p53_N239Y, and the transcriptionally active p53_S46F and p53_S121F. We have also produced novel combinations, p53_S46F_N239Y and p53_S46F_S121F for comparison and transcriptional activity analysis. Furthermore, we have identified two p53 mutants that are thermodynamically stable and with enhanced transcriptional activity compared to wild type p53. |
