Regulation of catalase expression in healthy and cancerous cells

Free Radic Biol Med. 2015 Oct:87:84-97. doi: 10.1016/j.freeradbiomed.2015.06.017. Epub 2015 Jun 25.

Abstract

Catalase is an important antioxidant enzyme that dismutates hydrogen peroxide into water and molecular oxygen. The catalase gene has all the characteristics of a housekeeping gene (no TATA box, no initiator element sequence, high GC content in promoter) and a core promoter that is highly conserved among species. We demonstrate in this review that within this core promoter, the presence of DNA binding sites for transcription factors, such as NF-Y and Sp1, plays an essential role in the positive regulation of catalase expression. Additional transcription factors, such as FoxO3a, are also involved in this regulatory process. There is strong evidence that the protein Akt/PKB in the PI3K signaling pathway plays a major role in the expression of catalase by modulating the activity of FoxO3a. Over the past decade, other transcription factors (PPARγ, Oct-1, etc.), as well as genetic, epigenetic, and posttranscriptional processes, have emerged as crucial contributors to the regulation of catalase expression. Altered expression levels of catalase have been reported in cancer tissues compared to their normal counterparts. Deciphering the molecular mechanisms that regulate catalase expression could, therefore, be of crucial importance for the future development of pro-oxidant cancer chemotherapy.

Keywords: Cancer; Catalase; Catalase promoter; Free radicals; Transcription factors; Transcription regulation.

Publication types

  • Review

MeSH terms

  • Antioxidants / metabolism
  • Binding Sites
  • Catalase / biosynthesis*
  • Catalase / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Promoter Regions, Genetic
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / genetics
  • Transcription, Genetic*

Substances

  • Antioxidants
  • DNA-Binding Proteins
  • Reactive Oxygen Species
  • Catalase