Structure and Function Essay -- Medical Research

First labelled an oncogene upon its discovery in 1979, p53 (or TP53 in humans), was correctly re-labelled a tumour suppressor a decade later following the discovery that the gene previously being studied was, ironically, a mutant. Now realised as the most common mutated gene, found in a staggering 50% of cancers, p53 is a keystone in the face of cancer. Its structure and functions continue to be delved into. Amino acids, genome stability, tumour suppression, iPS? Gene Structure 53 kilo-Daltons in size, 11 exons and 10 introns, p53 gene is located on chromosome 17. Using a clone isolated from a cDNA library of simian virus 40- transformed human fibroblasts, Mcbride et al. (1985), identified the location of p53 gene. Using karyotypic analysis and Southern analyses, they narrowed down the exact position of the p53 gene to the most distal band on the short arm of chromosome 17- the telomeric band 17p13. Structurally abundant in domains, p53 has three main functional domains and 393 amino acids in total. The first domain, the N-terminal (NH2 terminal) houses amino acids that are important in transactivation. In vivo, p53 requires amino acids F19, L22, and W23 found in the N-terminal for transcriptional activation (Lin et al., 1995). Present also, are the amino acid residues 22 and 23, although positive- regulators of transcriptional activity, are later to play a role in the negative-regulation of p53. In highlighting similarities between p53 protein-DNA interactions to other protein-DNA complexes, Cho et al. (1994), point out that p53 uses a loop packing at the NH2-terminal part of the alpha helix to make extra connections to the bases in the major groove of DNA. The C-terminal (carboxyl terminal) —61 important amino aci... ...anaka, S., 2009. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 460, 1132-1135. Lee, S., Elenbaas, B., Levine, A.J, and Griffith, J., 1995. p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell 81, 1013-1020. Levine, A.J., 1997. p53, the cellular gatekeeper for growth and division. Cell. 88, 323-331. Lin, J., Wu, X., Chen, J., Chang, A., and Levine, A.J., 1995. Functions of the the p53 protein growth regulation and tumour suppression. Cold Springs Harbour Symposia on Quantitative Biology LIX, 215-223. McBride, O.W., Merry, D.E., Oren, M., and Givol, D., 1985. The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17p13). Proc. Nat. Acad. Sci. 83, 130-134.