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The Guardian of the Genome (TP53) guided Aging and Cancer prevention!


DOI-LC06/04/19

Ramesh Kumar (PhD), LC Journal.

Correspondence to lcjournal@labstoclinic.com info@labstoclinic.com

A commentary from Science news posted recently, Opposite effect: Protein widely known to fight tumours also boosts cancer growth. The Original article published by Kim et al’., in Cancer cell, indicating context dependent broader functions of p531.

Many supportive
evidences are required to strengthen the above-mentioned statement. More precisely, when we say opposite effect of p53 (Science news January 31, 2019).

Growing body evidences suggest that cancer cells with a wild type p53 does not essentially function as tumour suppressor. In fact, p53 copy number determines its roles2,3.

In normal circumstances, cancer cells having 2 copies of p53 act as tumour suppressor, however altered copy numbers have been implicated for tumorigenic functions in the context dependent manner. Here, I would like to point out the earlier exciting research findings on significance of the p53 copy numbers which give us a clue on why elephants are protected from Cancer4.

The guardian of the genome "TP53" is connected through a complex signalling networks and finding an optimal signalling tune is not an easy task. Interestingly, studies have also suggested that a mild increase in p53 copy number can boost our DNA damage responses, checkpoints, immune functions and triggers protection from cellular aging to cancinogenesis.

I would like to take opportunity of mentioning an earlier exciting research from García-Cao et. al., on Super p53" mice, carrying p53-tg alleles in addition to the two endogenous alleles. These mice exhibit enhanced DNA damage responses. Interestingly, in contrast to wild type mice, "super p53" mice were significantly protected from carcinogenesis. Moreover, in contrast to earlier reported mice with constitutively active p53, "super p53" mice was protected of premature aging5.

Overall, in cancer cells if p53 not mutated, the copy number dictates the tumor heterogeneity. In healthy cells, optimal copy number is beneficial for normal cellular functions. Conflict of interest- The author declares this article as a personal opinion presented through the LC journal, and has no conflict of interest with any governmental and nongovernmental organisation.

References-

  1. Kim, J. et al. Wild-Type p53 Promotes Cancer Metabolic Switch by Inducing PUMA Dependent Suppression of Oxidative Phosphorylation. Cancer Cell, doi:10.1016/j.ccell.2018.12.012 (2019).
  2. Sulak, M. et al. Correction: TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants. Elife 5, doi:10.7554/eLife.24307 (2016).
  3. Sulak, M. et al. TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants. Elife 5, doi:10.7554/eLife.11994 (2016).
  4. Ewen Callaway. How elephants avoid cancer. Pachyderms have extra copies of a key tumour-fighting gene. Nature News 08 October 2015.
  5. García-Cao, et al. "Super p53" mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J. 2002;21(22):6225-35.