Hypoxic stabilization and proteolytic degradation of erythroid-specific 5-aminolevulinate synthase

Mohamed Abu-Farha, William G. Willmore

Research output: Contribution to journalArticlepeer-review

Abstract

Eukaryotes have acquired a broad range of post-translational modifications to place controls and checks on metabolic pathways. Included among these is hydroxylation. Hydroxylases catalyze the oxygen-, iron (II)-, ascorbate- and 2-oxoglutarate-dependent hydroxylation of protein substrates. Until recently, few studies examined hydroxylation as a post-translational modification, focusing primarily on hydroxylation of structural proteins such as collagen and elastin. With the discovery of hydroxylase-dependent destabilization of transcription factors, the role of hydroxylation in gene expression has renewed the interest in these enzymes. The paramount example of this is the hydroxylation of the transcription factor involved in hypoxic-inducible gene expression, Hypoxia-Inducible Factor-1 (HIF-1). The possibility exists that other proteins are hydroxylated in a manner similar to HIF-1 and are degraded and/or have altered enzymatic activities. These proteins may be involved in pathways that maintain oxygen homeostasis. A database search of potential targets of HIF-1 prolyl hydroxylases has revealed erythroid-specific 5-aminolevulinate synthase (ALAS2). Here we provide evidence that ALAS2 is broken down under normoxic conditions by the proteosome and that the prolyl-4-hydroxylase/E3 ubiquitin ligase pathway may be involved. The implications to oxygen sensing are discussed.

Original languageEnglish
Pages (from-to)71-78
Number of pages8
JournalInternational Congress Series
Volume1275
DOIs
Publication statusPublished - 1 Dec 2004

Keywords

  • E3 ubiquitin ligases
  • Erythroid-specific 5-aminolevulinate synthase
  • Hydroxylases
  • Hydroxylation
  • Hypoxia
  • Protein-protein interactions
  • Proteosomal degradation
  • von Hippel-Lindau protein

Fingerprint Dive into the research topics of 'Hypoxic stabilization and proteolytic degradation of erythroid-specific 5-aminolevulinate synthase'. Together they form a unique fingerprint.

Cite this