P53 pseudogene: potential role in heat shock induced apoptosis in a rat histiocytoma

Abstract

The p53 tumor suppressor gene is either non- functional or highly and frequently mutated in majority of cancers. In our study towards understanding cellular adaptations to stress using a rat histiocytic tumor model, we have identified mis-sense mutation in p53 that led to premature termination of translation at the carboxyl-termi- nus. Further, the cDNA isolated from heat stre- ssed cells producing two amplicons with cDNA specific primers (N-terminus) suggested occurrence of possible pseudogene(s). A comparative analysis between different tumor cell lines of rat origin and rat genomic DNA using p53 gene specific primers resulted in the amplification of a processed pseudogene and its positive interaction with wild type p53 probe on Southern blot analysis. The genomic DNA sequence analysis, and sequence comparison with cDNA discovered that the processed pseudogene lacks DNA binding domain and nuclear localization signal, however, contains the ribosomal entry and stop signals. Rat genome BLAST analysis of the pesudogene suggested chromosome-18 localization which was in addition to 14, 13, 10, 9 localization of the cDNA. In the interest of unraveling hidden dimensions of p53 tumor suppressor gene, our study explores the probability of p53 functional pseudogenes in rat histiocytoma.