Glucocorticoid receptor: translocation from the cytoplasm to the nuclei, chromatin and intranuclear chaperone cycles
Glucocorticoid receptor (GR) is a ligand-dependent transcription factor, involved in the regulation of hundreds of genes. In the absence of any ligand, GR resides in the cytoplasm where it is sequestered in a multimeric chaperone complex consisting of hsp90, hsp70, p23, Hop, FKBP51, FKBP52, etc. As...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2015-07-01
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| Series: | Вавиловский журнал генетики и селекции |
| Subjects: | |
| Online Access: | https://vavilov.elpub.ru/jour/article/view/405 |
| _version_ | 1797214182793281536 |
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| author | V. M. Merkulov N. V. Klimova T. I. Merkulova |
| author_facet | V. M. Merkulov N. V. Klimova T. I. Merkulova |
| author_sort | V. M. Merkulov |
| collection | DOAJ |
| description | Glucocorticoid receptor (GR) is a ligand-dependent transcription factor, involved in the regulation of hundreds of genes. In the absence of any ligand, GR resides in the cytoplasm where it is sequestered in a multimeric chaperone complex consisting of hsp90, hsp70, p23, Hop, FKBP51, FKBP52, etc. As part of this multiprotein complex, GR undergoes conformational changes that allow glucocorticoid hormone binding. Upon ligand binding, GR dissociates from chaperon complex and translocates into the nucleus, where it interacts with specific DNA sequences (GREs) in the regulatory regions of target genes and modulates their expression. Then unliganded GR is exported to the cytoplasm, completing the nuclear-cytoplasmic cycle. Recent evidence suggests that, in addition to this cycle, chromatin and chaperone GR cycles exist within the nuclei. The chromatin cycle implies repeated interactions of ligand-bound GR with GREs in the chromatin context lasting for few seconds. The chaperone cycle starts after dissociation of the hormone–receptor complex, when GR binds to the nuclear chaperone machinery. As a result, its hormone-binding affinity is regained. Upon hormone binding, GR releases from chaperon complex and binds to GREs again. It is assumed that the chaperone cycle is mainly responsible for prolonged GR retention in nuclei (half-life within 8–12 h upon steroid withdrawal). In this review, we summarize and critically analyze the published data on chromatin and intranuclear chaperone GR cycles. |
| first_indexed | 2024-03-07T16:07:36Z |
| format | Article |
| id | doaj.art-e7280ce206e1453180e0a2a84281e43a |
| institution | Directory Open Access Journal |
| issn | 2500-3259 |
| language | English |
| last_indexed | 2024-04-24T11:10:07Z |
| publishDate | 2015-07-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj.art-e7280ce206e1453180e0a2a84281e43a2024-04-11T15:30:55ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592015-07-0119325526310.18699/VJ15.032364Glucocorticoid receptor: translocation from the cytoplasm to the nuclei, chromatin and intranuclear chaperone cyclesV. M. Merkulov0N. V. Klimova1T. I. Merkulova2Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, РоссияФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, РоссияФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, РоссияGlucocorticoid receptor (GR) is a ligand-dependent transcription factor, involved in the regulation of hundreds of genes. In the absence of any ligand, GR resides in the cytoplasm where it is sequestered in a multimeric chaperone complex consisting of hsp90, hsp70, p23, Hop, FKBP51, FKBP52, etc. As part of this multiprotein complex, GR undergoes conformational changes that allow glucocorticoid hormone binding. Upon ligand binding, GR dissociates from chaperon complex and translocates into the nucleus, where it interacts with specific DNA sequences (GREs) in the regulatory regions of target genes and modulates their expression. Then unliganded GR is exported to the cytoplasm, completing the nuclear-cytoplasmic cycle. Recent evidence suggests that, in addition to this cycle, chromatin and chaperone GR cycles exist within the nuclei. The chromatin cycle implies repeated interactions of ligand-bound GR with GREs in the chromatin context lasting for few seconds. The chaperone cycle starts after dissociation of the hormone–receptor complex, when GR binds to the nuclear chaperone machinery. As a result, its hormone-binding affinity is regained. Upon hormone binding, GR releases from chaperon complex and binds to GREs again. It is assumed that the chaperone cycle is mainly responsible for prolonged GR retention in nuclei (half-life within 8–12 h upon steroid withdrawal). In this review, we summarize and critically analyze the published data on chromatin and intranuclear chaperone GR cycles.https://vavilov.elpub.ru/jour/article/view/405glucocorticoid receptormolecular chaperonesnucleichromatincycles. |
| spellingShingle | V. M. Merkulov N. V. Klimova T. I. Merkulova Glucocorticoid receptor: translocation from the cytoplasm to the nuclei, chromatin and intranuclear chaperone cycles Вавиловский журнал генетики и селекции glucocorticoid receptor molecular chaperones nuclei chromatin cycles. |
| title | Glucocorticoid receptor: translocation from the cytoplasm to the nuclei, chromatin and intranuclear chaperone cycles |
| title_full | Glucocorticoid receptor: translocation from the cytoplasm to the nuclei, chromatin and intranuclear chaperone cycles |
| title_fullStr | Glucocorticoid receptor: translocation from the cytoplasm to the nuclei, chromatin and intranuclear chaperone cycles |
| title_full_unstemmed | Glucocorticoid receptor: translocation from the cytoplasm to the nuclei, chromatin and intranuclear chaperone cycles |
| title_short | Glucocorticoid receptor: translocation from the cytoplasm to the nuclei, chromatin and intranuclear chaperone cycles |
| title_sort | glucocorticoid receptor translocation from the cytoplasm to the nuclei chromatin and intranuclear chaperone cycles |
| topic | glucocorticoid receptor molecular chaperones nuclei chromatin cycles. |
| url | https://vavilov.elpub.ru/jour/article/view/405 |
| work_keys_str_mv | AT vmmerkulov glucocorticoidreceptortranslocationfromthecytoplasmtothenucleichromatinandintranuclearchaperonecycles AT nvklimova glucocorticoidreceptortranslocationfromthecytoplasmtothenucleichromatinandintranuclearchaperonecycles AT timerkulova glucocorticoidreceptortranslocationfromthecytoplasmtothenucleichromatinandintranuclearchaperonecycles |