p53 is often mutated in human cancer. Recent studies have reported new roles of p53 in regulating metabolism, development, and differentiation.
p53 in cancer
p53 plays a significant role in coordinating stress responses, so it is no surprise that TP53 is the single most often mutated gene in human cancer, with partial or total loss of function happening in 60% of tumors.
When mutations occur in p53, it gives a selective advantage to cancer cells enabling them to prevent senescence and apoptosis, evade checkpoints for cell cycle, and proliferate under environments where normal cells are not able to do so.
What is more significant is the fact that colorectal cancer and cervical cancer, which are common cancers, have loss of function rates as high as 70% and 90%, respectively. Investigations performed in model systems have also demonstrated the tumor suppression role of p53 in a wide range of tissue and cell types. In addition, even cancers that can retain wild-type p53 evidence have shown that the p53 pathway can possibly go wrong at some other level.
In another study, a cancer predisposition syndrome called Li-Fraumeni syndrome was first described in 1969. In 1990 germline mutation in TP53 was attributed as causing this autosomal dominant syndrome which leads to the loss of wild-type p53 allele in cancer tissues1, 4, 5.
The role of p53 independent of tumor suppression
Recently, it has been reported that p53, besides tumor suppression, also has other different roles to play, such as its ability to regulate metabolism and different aspects of development and differentiation. In addition, there is growing evidence that p53 can have certain effect on the longevity and aging process in a role that is independent of tumor suppression.
While recent transgenic studies support this theory, no clear understanding is available on how p53 could affect these processes2, 3, 6.
- Levine AJ, Oren M. 2009. The first 30 years of p53: growing ever more complex. Nat Rev Cancer. 9(10):749-58. doi: 10.1038/nrc2723.
- Lane D, Levine A. 2010. p53 research: the past thirty years and the next thirty years. Cold Spring Harb Perspect Biol. 2(12):a000893. doi: 10.1101/cshperspect.a000893.
- Hasty P, Christy BA. 2013. p53 as an intervention target for cancer and aging. Pathobiol Aging Age Relat Dis. 3:22702. doi: 10.3402/pba.v3i0.22702.
- Garritano S, Inga A, Gemignani F, Landi S. 2013. More targets, more pathways and more clues for mutant p53. Oncogenesis. 2:e54. doi: 10.1038/oncsis.2013.15.
- Rivlin N, Brosh R, Oren M, Rotter V. 2011. Mutations in the p53 tumor suppressor gene: important milestones at the various steps of tumorigenesis. Genes Cancer. 2(4):466-74. doi: 10.1177/1947601911408889.
- Vousden KH, Prives C. 2009. Blinded by the light: the growing complexity of p53. Cell. 137(3):413-31. doi: 10.1016/j.cell.2009.04.037.
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