title: Control of steroid receptor dynamics and function by genomic actions of the cochaperones p23 and Bag-1L.
abstract: Molecular chaperones encompass a group of unrelated proteins that facilitate the correct assembly and disassembly of other macromolecular structures, which they themselves do not remain a part of. They associate with a large and diverse set of coregulators termed cochaperones that regulate their function and specificity. Amongst others, chaperones and cochaperones regulate the activity of several signaling molecules including steroid receptors, which upon ligand binding interact with discrete nucleotide sequences within the nucleus to control the expression of diverse physiological and developmental genes. Molecular chaperones and cochaperones are typically known to provide the correct conformation for ligand binding by the steroid receptors. While this contribution is widely accepted, recent studies have reported that they further modulate steroid receptor action outside ligand binding. They are thought to contribute to receptor turnover, transport of the receptor to different subcellular localizations, recycling of the receptor on chromatin and even stabilization of the DNA-binding properties of the receptor. In addition to these combined effects with molecular chaperones, cochaperones are reported to have additional functions that are independent of molecular chaperones. Some of these functions also impact on steroid receptor action. Two well-studied examples are the cochaperones p23 and Bag-1L, which have been identified as modulators of steroid receptor activity in nuclei. Understanding details of their regulatory action will provide new therapeutic opportunities of controlling steroid receptor action independent of the widespread effects of molecular chaperones.
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA (LC, MB) and Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany (AN, ACBC).
authors.forename: Laura
authors.initials: L
authors.lastname: Cato
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA (LC, MB) and Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany (AN, ACBC).
authors.forename: Antje
authors.initials: A
authors.lastname: Neeb
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA (LC, MB) and Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany (AN, ACBC).
authors.forename: Myles
authors.initials: M
authors.lastname: Brown
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA (LC, MB) and Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany (AN, ACBC).
authors.forename: Andrew C B
authors.initials: AC
authors.lastname: Cato
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D023281:Genomics / Q000379:methods*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D000071876:Prostaglandin-E Synthases; D011987:Receptors, Steroid / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D011987:Receptors, Steroid; D014157:Transcription Factors; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases
keywords: cellular transport; chaperones; nuclear receptors; steroid receptors