Monday, 30 April 2012

p53 “Guarding of the Genome”; Applications in Fertility and Cancer Treatments.

Nearly every cell in the human body undergoes cell reproduction. These cells are exposed to all kinds of environmental factors that cause mutations in the DNA in cells. Researchers have unravelled how the “Guardian of the Genome” plays a vital part in preserving cellular integrity. This new insight could lead to many potential applications in fertility treatments and cancer therapies.[2][4]

(Figure 1: Inhibitation of cell cyle in damaged cell due to p53, Source [1])

What is the “Guardian of the Genome”?
In a cells reproduction cycle, before a cell can divide, it is examined for any cancer-stimulating mutations by the key regulator gene, p53, which when present promotes transcription of proteins that suppress cell division.[2] Under these circumstances, if the mutation is repairable, it will then recommence its cell reproduction cycle without spreading the mutation. If the mutation is irreparable, p53 will commence apoptosis – automated cell death.[1] This vital process is important in protecting the wellbeing of the genome; hence p53’s title “Guardian of the Genome”. [2]

p53 uses in Contraception and Fertility Applications.
Recently, research at Yale University has revealed that p53 is controlled by Pumilo 1 during Spermatogenesis – sperm cell formation. Pumilo 1, which in sperm production, controls eight RNA molecules that interact with p53.[2] This was discovered through the Yale scientists study of sperm production in mice. In their experiment, when Pumilo 1 is genetically removed, p53 is activated in a form of overdrive and commences apoptosis in many sperm cells, leading to reduce sperm count and reduced fertility.[3] This relationship between p53 and Pumilo 1 could be used as a form of contraception. The same principle could be adapted for individuals that suffer from natural low sperm counts, by possibly reducing the amount of p53 through Pumilo 1 manipulation. However, this scenario could lead to cancer-stimulating mutation being overlooked and even lead to deformations in sperm and potential offspring.

(Figure 2:Compaison between Active p53, Inactive p53 and Reactivation of p53, Source [5])

Cancer therapies by reviving deactivated p53 gene.
With p53 being such an important aspect in natural prevention of cancers, lack of or defection in this regulator could lead to catastrophic consequences, with approximately over half of human cancers having mutated p53.[1][4] MIT Cancer researchers are currently working on a drug to manipulate p53 to supress tumours.  In 2010 they genetically engineered a variety of mouse with inactive forms of the p53 gene that could be reactivated once a tumour had developed. [4]Through their experimentation they discovered that the more malignant the stage of cancer, the higher the success rate of apoptosis in the cell through reactivated p53. Benign tumours unlike malignant varieties don’t exhibit symptoms such as uncontrolled growth and therefore don’t attract the same level of attention of p53.[4] It’s not a cure for cancer but it may well be another potential tool in cancer treatment.

In conclusion, p53 has earned its title as the “Guardian of the Genome”. However, this particular key regulator, and those in conjunction with it, could lead to many applications in fertility treatment; birth control and cancer therapies. Although these applications are not yet able to put in to practise, further research is on the way to showing some promising discoveries.

Reference List
  1. Reece, J. B., Meyers, N., Urry, L.A., Cain, M.L., Wasserman, S.A., Minorsky, P.V., Jackson, R.B., Cooke, B.N., 2011. Campbell Biology. 9th (Australian Version) ed. Pearson Australia Group Pty Ltd.
  2. Hathaway, B 2012, Secret of sperm quality control revealed by Yale scientists, media release, 16 February,  Yale News, viewed 2 March 2012,  < >.
  3. Haifan, L., Dong , C., Wei, Z., Aiping, L., Katherine, U., Hongyu, Z., 2012, Pumilio 1 Suppresses Multiple Activators of p53 to Safeguard Spermatogenesis, media release, 16 February, Current Biology, viewed 2 March 2012, <>.
  4. Trafton, A., 2010, Biologists find that restoring the gene for cancer protein p53 slows spread of advanced tumours, media release, 25 November 2010, MIT media relations, viewed on 8 March 2012, <>.
  5. 2008, p53 image, media release, 5 March 1998, viewed 8 March 2012, <>.

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