Recycling and Desensitization of Glucocorticoid Receptors in v-mosTransformed Cells Depend on the Ability of Nuclear Receptors to Modulate Gene Expression
Autor: | Ming Qi, Laurie J. Stasenko, Donald B. DeFranco |
---|---|
Rok vydání: | 1990 |
Předmět: |
Agonist
Cytoplasm endocrine system medicine.drug_class medicine.medical_treatment Retroviridae Proteins Oncogenic Fluorescent Antibody Technique Gene Expression Oncogene Proteins v-mos Receptors Cell Surface Biology Dexamethasone Translocation Genetic Receptors Glucocorticoid Endocrinology Glucocorticoid receptor medicine Animals Receptor Molecular Biology Cell Line Transformed PELP-1 Cell Nucleus General Medicine Rats Cell biology Mifepristone Cell nucleus Steroid hormone medicine.anatomical_structure Nuclear receptor Biochemistry hormones hormone substitutes and hormone antagonists |
Zdroj: | Molecular Endocrinology. 4:455-464 |
ISSN: | 1944-9917 0888-8809 |
Popis: | In v-mos transformed cells, glucocorticoid receptor (GR) proteins that bind hormone agonist are not efficiently retained within nuclei and redistribute to the cytoplasmic compartment. These cytoplasmic desensitized receptors cannot be reutilized and may represent trapped intermediates derived from GR recycling. We have used the glucocorticoid antagonist RU486 to examine whether v-mos effects can be exerted on any ligand-bound GR. In the rat 6m2 cell line that expresses a temperature-sensitive p85gag-mos oncoprotein, RU486 is a complete antagonist and suppresses dexamethasone induction of metallothionein-1 mRNA at equimolar concentrations. Using indirect immunofluorescence, we observe efficient nuclear translocation of GR in response to RU486 treatment in either the presence or absence of v-mos oncoproteins. However, in contrast to the redistribution of agonist-bound nuclear receptors to the cytoplasm of v-mos-transformed cells, RU486-bound GRs are efficiently retained within nuclei. Interestingly, withdrawal of RU486 does not lead to efficient depletion of nuclear GR in either nontransformed or v-mos transformed cells. It is only after the addition of hormone agonist to RU486 withdrawn v-mos-transformed cells that GRs are depleted from nuclei and subsequently redistributed to the cytoplasm. Thus, only nuclear GRs that are agonist-bound and capable of modulating gene activity can be subsequently processed and recycled into the cytoplasm. |
Databáze: | OpenAIRE |
Externí odkaz: |