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 un-derstanding 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 oc-currence of possible pseudogene(s). A com-parative analysis between different tumor cell lines of rat origin and rat genomic DNA using p53 gene specific primers resulted in the ampli-fication of a processed pseudogene and its positive interaction with wild type p53 probe on Southern blot analysis. The genomic DNA se-quence analysis, and sequence comparison with cDNA discovered that the processed pseu-dogene lacks DNA binding domain and nuclear localization signal, however, contains the ribo-somal entry and stop signals. Rat genome BLAST analysis of the pesudogene suggested chromosome-18 localization which was in addi-tion 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.