NRF2 and p53

Januses in cancer?

Barak Rotblat, Gerry Melino, Richard A. Knight

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

The transcription factor nuclear factor (erythroid-derived 2)-like 2, also known as NFE2L2 or NRF2, is a master regulator of the anti-oxidative stress response and positively controls the expression of a battery of anti-oxidative stress response proteins and enzymes implicated in detoxification and glutathione generation. Although its detoxifying activity is important in cancer prevention, it has recently been shown that cancer cells also exploit its protective functions to thrive and resist chemotherapy. NRF2 was also shown to the pentose phosphate pathway and glutaminolysis, which promotes purine synthesis for supporting rapid proliferation and glutathione for providing anti-oxidative stress protection. Evidence obtained from cancer patients and cell lines suggest that NRF2 is highly active in a variety of human cancers and is associated with aggressiveness. p53 is a tumor suppressor that also promotes an anti-oxidative stress metabolic program and glutaminolysis. Here we will discuss the similarities between NRF2 and p53 and review evidence that p53 might be exploited by cancer cells to gain protection against oxidative stress, as is the case for NRF2. We discuss findings of co-regulation between these transcription factors and propose possible therapeutic strategies that can be used for treatment of cancers that harbor WT p53 and express high levels of NRF2.

Original languageEnglish
Pages (from-to)1272-1283
Number of pages12
JournalOncotarget
Volume3
Issue number11
Publication statusPublished - 2012

Fingerprint

Oxidative Stress
Neoplasms
Glutathione
NF-E2 Transcription Factor
Pentose Phosphate Pathway
Heat-Shock Proteins
Transcription Factors
Drug Therapy
Cell Line
Enzymes
Therapeutics

Keywords

  • BPTES
  • Brusatol
  • BSO
  • Chemotherapy
  • KEAP1
  • MDM2
  • Metabolism
  • NADPH
  • NQO1
  • P21
  • P53
  • P73
  • Piperlongumine
  • Proteasome
  • ROS
  • TIGAR

ASJC Scopus subject areas

  • Oncology

Cite this

Rotblat, B., Melino, G., & Knight, R. A. (2012). NRF2 and p53: Januses in cancer? Oncotarget, 3(11), 1272-1283.

NRF2 and p53 : Januses in cancer? / Rotblat, Barak; Melino, Gerry; Knight, Richard A.

In: Oncotarget, Vol. 3, No. 11, 2012, p. 1272-1283.

Research output: Contribution to journalArticle

Rotblat, B, Melino, G & Knight, RA 2012, 'NRF2 and p53: Januses in cancer?', Oncotarget, vol. 3, no. 11, pp. 1272-1283.
Rotblat B, Melino G, Knight RA. NRF2 and p53: Januses in cancer? Oncotarget. 2012;3(11):1272-1283.
Rotblat, Barak ; Melino, Gerry ; Knight, Richard A. / NRF2 and p53 : Januses in cancer?. In: Oncotarget. 2012 ; Vol. 3, No. 11. pp. 1272-1283.
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