The document discusses regulation of p53 activities in cancer. P53 regulates genes that induce apoptosis, cell cycle arrest, or senescence in response to stress. Many cancers have mutations in the TP53 gene, resulting in mutant p53 proteins that have lost wild type tumor suppressor functions and gained oncogenic properties. Emerging evidence suggests mutant p53 proteins express these new functions by interacting with other proteins to enhance or inhibit their activities, contributing to cancer development. Targeting mutant p53 proteins is a promising new approach for cancer therapies.

1. REGULATION OF P53 ACTVITIES IN CANCER
INTRODUCTION: The pivotal role of the transcriptional factor p53 in tumor prevention is widely known. P53 regulates its target genes
generating different biological processes in response to stress: apoptosis, cell cycle arrest or senescence (Liu et al, 2015). A significant
presence of TP53 mutations has been displayed in several types of cancer, leading to mutant p53 proteins. These mutant p53s have both
lost wild type p53 activity and gained functions that contribute to the development of cancer (Muller and Vousden, 2014). Some of the
emerging molecular mechanisms through which mutant p53 proteins can express these oncogenic functions are presented below.
Francesca Savarese, Faculty of Science and Technology, Applied Molecular Biology,
University of Westminster, 115 New Cavendish St., London, UK
CONCLUSIONS: The high presence of mutant p53s in cancer cells makes these proteins extremely appealing therapeutic targets.
Moreover the efficacy of inhibiting the activity of these mutant p53s or even restoring some wild type functions represents a hope in the
upcoming research involving the development of new useful therapies in a wide range of cancer.
REFERENCES: Goldstein, I., Marcel V., Olivier, M., Oren, M., Rotter V. and Hainaut P. (2011). Understanding wild-type and mutant p53 activities in human cancer: new landmarks on the way to targeted therapies. Cancer
Gene Therapy 18, 2-11. Available from https://www.google.it/url?sa=t&rct=j&q=&esrc=s&source=web&cd=3&cad=rja&uact=8&ved=0CC8QFjACahUKEwjb94Kh-
YPJAhUB7BQKHW_7CJk&url=http%3A%2F%2Fwww.nature.com%2Fcgt%2Fjournal%2Fv18%2Fn1%2Fabs%2Fcgt201063a.html&usg=AFQjCNGmDw_I01olyRKouNEaVvAn8YH0WA [accessed 10 November 2015]
Liu, J., Zhang, C., Hu W., Feng Z. (2015). Tumor suppressor p53 and its mutant in cancer metabolism. Cancer Letters, 356, (2 Pt A), 197-203. Available from http://dx.doi.org/10.1016/j.canlet.2013.12.025 [accessed 9
November 2015]
Muller, P. A. J. and Vousden, K. H. (2014). Mutant p53 in Cancer: new Functions and Therapeutic Opportunities. Cancer cell 25, 17 March. Available from http://dx.doi.org/10.1016/j.ccr.2014.01.021 [accessed 9 November
2015]
Muller, P. A. J. and Vousden, K. H. (2013). P53 mutations in cancer. Nature Cell Biology, 15, 2-8. Available from
https://www.google.it/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=0CCAQFjAAahUKEwidpuuM_YPJAhUIxxQKHWzeA5U&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F23263379&usg
=AFQjCNFd5Y3BlpOOgth_ThKepUKSUjfhpA [accessed 9 November 2015]
FIG.2 Properties of mutant p53 proteins. Missense mutations at hot-spot
codons located in the DNA binding domain of p53. Three types of p53
mutant: DN, LOF, GOF.
FIG.1 (a) P53 domain structure, (b) P53 activation
FIG.5 Strategies that Are Currently Being Explored to Target Mutant p53.
FIG.3 Models of mechanisms through which mutant p53 functions. As part of its gain
of function mutant p53 interact with different proteins to ehance or ihnibit their
activities. TF, trancription factor; X, any protein other than a trancription factor or
transcriptional cofactor; MAR, matrix attachment region DNA elements; mp53,
mutant p53.
FIG.4 Mutant p53 binds to numerous proteins to enhance or inhibit their
function.
(a) Mutant p53 ehnances SBRP function to increase sterol biosynthesis leading
to enhanced anchorage- indepedent growth and disruption of mammary
tissue architecture.
(b) In response to DNA damage TopBP1 e PLK2 facilitate the recruitment of
p53 to NF-Y leading to incresead expression of genes involved in
proliferation and chemioresistence.