Cellular respiration and tumor suppressor genes

Luis F. Gonzalez-Cuyar, Fabio Tavora, Iusta Caminha, George Perry, Mark A. Smith, Rudy J. Castellani*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

More than 70 years have passed since Dr. Otto Warburg first documented that cancer cells relied primarily on aerobic glycolysis. However, it was not until the late-1980s and 1990s when cellular respiration, cellular oxygen sensors, and hypoxia were convincingly related to tumorigenesis and tumor progression. With the discovery of hypoxia inducible factor (HIF-1) and its target genes, the relationship that was once weak has become very strong. The expression of the HIF-1 molecule has been proved to occur by hypoxic stress and confers an adaptation advantage, upregulating genes involved in angiogenesis and glycolysis among others. It has been reported that HIF-1 is under the control of tumor suppressor genes such as the von Hippel-Lindau (pVHL) protein, which, under normoxia, ubiquitinates HIF-1 for proteosomal degradation. Additionally, the tumor suppressor gene p53 has been reported to be stabilized by HIF-1 and inhibits Mdm2-dependent degradation. Recently, it was reported that synthesis of cytochrome c oxidase, a regulator of the cytochrome c oxidase pathway, is a p53 target. Moreover, interactions of pVHL and p53 stabilize p53 and permits p53-mediated apoptosis. The aim of this chapter is to outline how the cellular microenvironment affects cellular respiration and perhaps induces tumorigenesis, as well as to discuss ways in which tumor suppressor genes are also involved.

Original languageEnglish (US)
Title of host publicationCellular Respiration and Carcinogenesis
PublisherHumana Press
Pages131-144
Number of pages14
ISBN (Print)9781934115077
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Cellular respiration
  • Hypoxia inducible factor
  • p53
  • Tumor suppressor
  • Von Hippel-Lindau

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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