All tags p53 Roles of p53

Roles of p53

p53 is frequently mutated in human cancer. Recently new roles in regulating metabolism, differentiation and development have been reported.

p53 in cancer

Not unexpectedly, given the significant role played by p53 in coordinating stress responses, TP53 is the single most frequently mutated gene in human cancer, with partial or complete loss of function occurring in 60% of tumors.

Mutations in p53 confer a selective advantage on the tumor cells, allowing them to evade cell cycle checkpoints, avoid apoptosis and senescence, and proliferate under conditions where normal cells cannot.

Even more striking is the fact that some common cancers such as cervical cancer and colorectal cancer show loss of function rates as high as 90% and 70% respectively. Studies in model systems have further demonstrated a role for p53 in tumor suppression in a host of different cell and tissue types.

Furthermore, even in the case of cancers that retain a wild-type p53 there is evidence that the p53 pathway can malfunction at some other level.

Also, in 1990, the Li-Fraumeni syndrome, a cancer predisposition syndrome was first described. This is an autosomal dominant syndrome, caused by germline mutation in TP53 and results in the loss of the wild-type p53 allele in tumor tissues (1, 4 and 5).

The role of p53 independent of tumor suppression

New roles for p53 have recently been reported including its ability to regulate metabolism and various aspects of differentiation and development.

It is becoming clear that p53 can also exert some influence on the aging process and longevity in a role independent from that of a tumor suppressor.

There is mounting evidence for this theory from some recent transgenic studies, but a clear lack of understanding into how p53 could influence these processes is still in its infancy (2, 3, and 6).

References

  • 1. 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.
  • 2. 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.
  • 3. 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.
  • 4. 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.
  • 5. 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.
  • 6. 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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