Degradation of Thyroid Hormone Receptor Beta 1: Existence of Stable and Unstable Forms
Autor: | Mylène Brunelle, Tania Fayad, Marie-France Langlois |
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Rok vydání: | 2011 |
Předmět: |
Cell Nucleus
Proteasome Endopeptidase Complex education.field_of_study Thyroid hormone receptor medicine.diagnostic_test Endocrinology Diabetes and Metabolism Population Thyroid Hormone Receptors beta Thyroid Hormone Receptor beta-1 Biology Cycloheximide chemistry.chemical_compound Endocrinology Biochemistry Western blot chemistry Nuclear receptor Enzyme Stability medicine Protein biosynthesis education Cellular compartment |
Zdroj: | Thyroid. 21:311-318 |
ISSN: | 1557-9077 1050-7256 |
DOI: | 10.1089/thy.2009.0363 |
Popis: | 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.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.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.Our findings introduce novel evidence suggesting that stable and unstable forms of TRβ1, which might have distinct functions, co-exist in cells. |
Databáze: | OpenAIRE |
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