Linked Life Data

20555024

Source:http://linkedlifedata.com/resource/pubmed/id/20555024

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-7-27
pubmed:abstractText
Ectopic ACTH syndrome (EAS) accounts for 10-15% of cases of Cushing's syndrome and is mostly caused by small cell lung cancers or thymic carcinoids. EAS is characterized by tumoral cortisol resistance, whose underlying mechanism remains unknown. In this study, we reported that silencing mediator of retinoic acid and thyroid hormone receptors (SMRT), a major nuclear corepressor, was aberrantly expressed in ACTH-secreting thymic carcinoids. Overexpression and knockdown of SMRT in the ACTH-secreting AtT-20 cell line demonstrated that SMRT participated in the negative feedback of dexamethasone-mediated suppression of proopiomelanocortin. Posttranslational modification by the small ubiquitin-like modifiers (SUMO), i.e. SUMOylation plays an important role in fine-tuning transcriptional activities. SUMOylation of SMRT was observed in dexamethasone-resistant cell lines. Moreover, overexpression of the deSUMOylation enzyme enhanced the suppression of proopiomelanocortin by dexamethasone in AtT-20 cells. An evolutionarily conserved consensus SUMOylation site was identified close to the histone deacetylase 3 recruiting domain of SMRT, which might interfere with the recruiting process. These results suggested that aberrant expression and modification of SMRT might be involved in the pathogenesis of tumoral cortisol resistance. A therapeutic approach targeting SMRT SUMOylation might be developed for EAS patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1945-7170
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
151
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3697-705
pubmed:meshHeading
pubmed-meshheading:20555024-ACTH Syndrome, Ectopic, pubmed-meshheading:20555024-Animals, pubmed-meshheading:20555024-Carcinoid Tumor, pubmed-meshheading:20555024-Cells, Cultured, pubmed-meshheading:20555024-Drug Resistance, pubmed-meshheading:20555024-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20555024-Histone Deacetylases, pubmed-meshheading:20555024-Humans, pubmed-meshheading:20555024-Hydrocortisone, pubmed-meshheading:20555024-Mice, pubmed-meshheading:20555024-Nuclear Receptor Co-Repressor 2, pubmed-meshheading:20555024-Pro-Opiomelanocortin, pubmed-meshheading:20555024-Protein Processing, Post-Translational, pubmed-meshheading:20555024-RNA, Small Interfering, pubmed-meshheading:20555024-SUMO-1 Protein, pubmed-meshheading:20555024-Thymus Neoplasms, pubmed-meshheading:20555024-Transfection
pubmed:year
2010
pubmed:articleTitle
Aberrant expression and modification of silencing mediator of retinoic acid and thyroid hormone receptors involved in the pathogenesis of tumoral cortisol resistance.
pubmed:affiliation
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't