Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

p53

  • Daniel Menendez
  • Thuy-Ai Nguyen
  • Michael A. Resnick
  • Carl W. Anderson
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_57

Synonyms

 FLJ92943;  LFS1;  TP53;  TRP53

Historical Background

As the major tumor suppressor in multicellular organisms, p53 is one of the most intensively studied human proteins (over 80,000 publications including nearly 10,000 reviews) because it is critical for maintaining genomic stability, cellular homeostatic processes in response to multiple stresses, and suppressing cancers. The p53 protein is a tetrameric, sequence-specific, DNA-binding transcription factor, stabilized and activated in response to genotoxic and non-genotoxic stresses; estimates are that activation of p53 directly or indirectly induces or represses the expression of about 3,000 genes (about 10% of human genes). These genes coordinate the cellular response to protect cells and/or the organism from damage (Riley et al. 2008). When possible they promote a return to homeostasis by arresting the cell cycle and inducing repair; by altering cellular metabolism; by initiating apoptosis, a program of cell death; or by...
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.

References

  1. Aubrey BJ, Strasser A, Kelly GL. Tumor-suppressor functions of the TP53 pathway. Cold Spring Harbor Perspect Med. 2016;6.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Bieging K, Mello SS, Attardi LD. Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer. 2014;14:359–70.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Candi E, Agostini M, Melino G, Bernassola F. How the TP53 family proteins TP63 and TP73 contribute to tumorigenesis: regulators and effectors. Hum Mutat. 2014;35:702–14.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Donehower LA, Lozano G. 20 years studying p53 functions in genetically engineered mice. Nat Rev Cancer. 2009;9:831–41.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Harris SL, Levine AJ. The p53 pathway: positive and negative feedback loops. Oncogene. 2005;24:2899–908.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Joerger AC, Fersht AR. The p53 pathway: origins, inactivation in cancer, and emerging therapeutic approaches. Annu Rev Biochem. 2016;85:375–404.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Lane DP. Cancer. p53, guardian of the genome. Nature. 1992;358:15–6.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Levine AJ. The common mechanisms of transformation by the small DNA tumor viruses: the inactivation of tumor suppressor gene products: p53. Virology. 2009;384:285–93.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Levine AJ, Oren M. The first 30 years of p53: growing ever more complex. Nat Rev Cancer. 2009;9:749–58.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Lu WJ, Amatruda JF, Abrams JM. p53 ancestry: gazing through an evolutionary lens. Nat Rev Cancer. 2009;9:758–62.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Meek DW, Anderson CW. Posttranslational modification of p53: cooperative integrators of function. In: Levine AJ, Lane D, editors. Cold spring harbor perspectives in biology, volume on the p53 family. New York: Cold Spring Harbor Laboratory Press; 2010. p. 81–96.Google Scholar
  12. Meek DW, Hupp TR. The regulation of MDM2 by multisite phosphorylation – opportunities for molecular-based intervention to target tumors? Semin Cancer Biol. 2010;20:19–28.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Menendez D, Inga A, Resnick MA. The expanding universe of p53 targets. Nat Rev Cancer. 2009;9:724–37.PubMedCrossRefGoogle Scholar
  14. Nguyen TA, Menendez D, Resnick MA, Anderson CW. Mutant TP53 posttranslational modifications: challenges and opportunities. Hum Mutat. 2014;35:738–55.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. In: Levine AJ, Lane D, editors. Cold spring harbor perspectives in biology, volume on the p53 family. New York: Cold Spring Harbor Laboratory Press; 2010. p. 123–40.Google Scholar
  16. Perry ME. The regulation of the p53-mediated stress response by MDM2 and MDM4. In: Levine AJ, Lane D, editors. Cold spring harbor perspectives in biology, volume on the p53 family. New York: Cold Spring Harbor Laboratory Press; 2010. p. 97–108.Google Scholar
  17. Riley T, Sontag E, Chen P, Levine A. Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol. 2008;9:402–12.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Shetzer Y, Molchadsky, A, Rotter V. Oncogenic mutant p53 gain of function nourishes the vicious cycle of tumor development and cancer stem-cell function. Cold Spring Harb Perspect Med 2016 doi:10.1101/cshperspect.a026203.CrossRefPubMedGoogle Scholar
  19. Vaseva AV, Moll UM. The mitochondrial p53 pathway. Biochim Biophys Acta. 2009;1787:414–20.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Vousden KH, Prives C. Blinded by the light: the growing complexity of p53. Cell. 2009;137:413–31.PubMedCrossRefGoogle Scholar
  21. Whibley C, Pharoah D, Hollstein M. p53 polymorphisms: cancer implications. Nat Rev Cancer. 2009;9:95–107.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Daniel Menendez
    • 1
  • Thuy-Ai Nguyen
    • 1
  • Michael A. Resnick
    • 1
  • Carl W. Anderson
    • 1
    • 2
  1. 1.Chromosome Stability Group, Genome Integrity and Structural Biology LaboratoryNational Institute of Environmental Health Sciences, NIHResearch Triangle ParkUSA
  2. 2.Biology DepartmentBrookhaven National LaboratoryUptonUSA