title: The hinge region in androgen receptor control.
abstract: The region between the DNA-binding domain and the ligand-binding domain of nuclear receptors is termed the hinge region. Although this flexible linker is poorly conserved, diverse functions have been ascribed to it. For the androgen receptor (AR), the hinge region and in particular the (629)RKLKKL(634) motif, plays a central role in controlling AR activity, not only because it acts as the main part of the nuclear translocation signal, but also because it regulates the transactivation potential and intranuclear mobility of the receptor. It is also a target site for acetylation, ubiquitylation and methylation. The interplay between these different modifications as well as the phosphorylation at serine 650 will be discussed here. The hinge also has an important function in AR binding to classical versus selective androgen response elements. In addition, the number of coactivators/corepressors that might act via interaction with the hinge region is still growing. The importance of the hinge region is further illustrated by the different somatic mutations described in patients with androgen insensitivity syndrome and prostate cancer. In conclusion, the hinge region serves as an integrator for signals coming from different pathways that provide feedback to the control of AR activity.
authors.affiliation: Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Campus Gasthuisberg O&N1, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Clinckemalie
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Frank
authors.initials: F
authors.lastname: Claessens
mesh_terms: D000107:Acetylation; D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D008745:Methylation; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D011944:Receptors, Androgen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D015533:Transcriptional Activation; D054875:Ubiquitination
chemical_list: D004268:DNA-Binding Proteins; D010455:Peptides; D011944:Receptors, Androgen