p53: the stress responder
TP53, a tumor suppressor gene, and p53, its protein product, were first discovered in 1979 and since then, they have been the subject of intense research in the field of cancer biology.
There have been major developments in knowledge and growing complexities, with over 100 genetic or physical interactions identified to date. However, despite these advances, the canonical role of p53 protein remains similar to that of a tumor suppressor protein, which responds when damage occurs to DNA.
Nonetheless, the p53 protein is known to coordinate various cellular functions in response to many different stresses such as:
- telomere shortening
- oncogene activation
- viral infection
- oxidative stress
- ribosomal stress
- metabolic stress
However, decoding and breaking down the mechanisms through which the p53 coordinates these functions continues to be part of in-depth investigations.
p53 as a transcription factor
As a transcription factor, p53 activates a host of transcriptional targets in response to cellular stress, and mediates the required response. The types of responses include:
- DNA repair
- cell cycle arrest
- altered metabolism
- anti-angiogenic effects
- anti-oxidant effects
As part of the pursuit of knowledge to expose the mysteries of p53, a new study has shed some light on its tumor suppressive functions. It was shown that in T-cell lymphomas, p53 executes a range of functions based on its developmental and cellular context4.
p53 and its transcription-independent roles
In addition, the p53 protein mediates transcription-independent functions that include DNA repair, regulation of microRNA processing, ribosome biogenesis, and mitochondrial protein survival5.
- 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.
- 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.
- Mills KD. 2013. Tumor suppression: putting p53 in context. Cell cycle. 12(22):3461-2. doi: 10.4161/cc.26806.
- 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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