title: Degradation of thyroid hormone receptor beta 1: existence of stable and unstable forms.
abstract: BACKGROUND
  The degradation of many nuclear receptors is controlled by ligand-binding and mediated by the ubiquitin-proteasome pathway. However, the mechanisms implicated in thyroid hormone receptor (TR) degradation remain unclear. Our objective was to define the kinetics, mechanisms, and sub-cellular fractions involved in TRs degradation.
  
  
  METHODS
  We used pulse-chase analyses, time-course experiments carried out in presence of cycloheximide (to inhibit new protein synthesis), and biochemical fractionation with Western blot analyses to determine the kinetics of the degradation of the TRβ isoform, TRβ1, in transiently transfected QBI-HEK 293A cells.
  
  
  RESULTS
  We observed that TRβ1 degradation is mediated by the proteasome pathway. Also, the kinetics of TRβ1 degradation is atypical due to the co-existence of more than one TRβ1 population, located in different cellular compartments and having different stability profiles. Moreover, TRβ1 degradation was unaffected by a mutation in its putative PEST motif, which confers turnover of other proteins.
  
  
  CONCLUSIONS
  Our findings introduce novel evidence suggesting that stable and unstable forms of TRβ1, which might have distinct functions, co-exist in cells.
authors.affiliation: Département de Médecine, Service d'endocrinologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: Mylène
authors.initials: M
authors.lastname: Brunelle
authors.forename: Tania
authors.initials: T
authors.lastname: Fayad
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Langlois
mesh_terms: D002467:Cell Nucleus / Q000201:enzymology; D004795:Enzyme Stability; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism*
chemical_list: D037042:Thyroid Hormone Receptors beta; D046988:Proteasome Endopeptidase Complex