title: Protein degradation and iron homeostasis.
abstract: Regulation of both systemic and cellular iron homeostasis requires the capacity to sense iron levels and appropriately modify the expression of iron metabolism genes. These responses are coordinated through the efforts of several key regulatory factors including F-box and Leucine-rich Repeat Protein 5 (FBXL5), Iron Regulatory Proteins (IRPs), Hypoxia Inducible Factor (HIF), and ferroportin. Notably, the stability of each of these proteins is regulated in response to iron. Recent discoveries have greatly advanced our understanding of the molecular mechanisms governing iron-sensing and protein degradation within these pathways. It has become clear that iron's privileged roles in both enzyme catalysis and protein structure contribute to its regulation of protein stability. Moreover, these multiple pathways intersect with one another in larger regulatory networks to maintain iron homeostasis. This article is part of a Special Issue entitled: Cell Biology of Metals.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
authors.forename: Joel W
authors.initials: JW
authors.lastname: Thompson
authors.forename: Richard K
authors.initials: RK
authors.lastname: Bruick
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D064451:Hepcidins; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D010100:Oxygen / Q000378:metabolism; D055550:Protein Stability; D059748:Proteolysis; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000098742:Ferroportin
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D044783:F-Box Proteins; C521741:FBXL5 protein, human; D064451:Hepcidins; D051793:Hypoxia-Inducible Factor 1; D035925:Iron-Regulatory Proteins; D000098742:Ferroportin; D007501:Iron; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D010100:Oxygen