All tags p53 p53: an introduction

p53: an introduction

p53 is best known as a tumor suppressor protein responding to DNA damage, but it also coordinates a range of other functions.

p53: the stress responder

The tumor suppressor gene TP53 and its protein product p53 were discovered in 1979, and have since been the topic of intense study in the cancer biology field.

Despite the advances in knowledge and increased complexities - to date more than 100 physical or genetic interactions have been identified - the canonical role of p53 remains as that of a tumor suppressor protein that responds to DNA damage.

However, p53 is now known to coordinate diverse cellular functions in response to a range of different stresses including oncogene activation, telomere shortening, hypoxia, metabolic stress, ribosomal stress, oxidative stress and viral infection, but deciphering the mechanisms by which it does this remains part of intensive investigations (1, 2, and 3).

p53 as a transcription factor

p53 is a transcription factor, and in response to cellular stress a multitude of transcriptional targets are activated, and mediate the desired response.

The range of responses includes cell cycle arrest, DNA repair, altered metabolism, anti-oxidant effects, anti-angiogenic effects, autophagy, senescence and apoptosis.

As part of the on-going quest for knowledge to unravel the secrets of p53, a recent study provides some new clues for its tumor suppressive functions. They show, in T-cell lymphomas, that it performs different functions depending on its cellular and developmental context (4).

p53 and its transcription-independent roles

p53 also mediates transcription-independent functions that include regulating microRNA processing, DNA repair, mitochondrial protein survival, and ribosome biogenesis (5).


References

  • 1. Nag S, Qin J, Srivenugopal KS, Wang M, Zhang R. 2013. The MDM2-p53 pathway revisited. J Biomed Res. 27(4):254-71. doi: 10.7555/JBR.27.20130030.
  • 2. 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.
  • 3. 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.
  • 4. Mills KD. 2013. Tumor suppression: putting p53 in context. Cell cycle. 12(22):3461-2. doi: 10.4161/cc.26806.
  • 5. 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.
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