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Titolo:
A new human MR splice variant is a ligand-independent transactivator modulating corticosteroid action
Autore:
Zennaro, MC; Souque, A; Viengchareun, S; Poisson, E; Lombes, M;
Indirizzi:
Univ Paris 07, INSERM, U478, F-75870 Paris 18, France Univ Paris 07 Paris France 18 07, INSERM, U478, F-75870 Paris 18, France
Titolo Testata:
MOLECULAR ENDOCRINOLOGY
fascicolo: 9, volume: 15, anno: 2001,
pagine: 1586 - 1598
SICI:
0888-8809(200109)15:9<1586:ANHMSV>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN MINERALOCORTICOID RECEPTOR; HUMAN GLUCOCORTICOID RECEPTOR; MESSENGER-RIBONUCLEIC-ACID; ESTROGEN-RECEPTOR; BINDING DOMAIN; TRANSCRIPTIONAL ACTIVATION; ALTERNATIVE PROMOTERS; NUCLEAR RECEPTORS; CARDIAC FIBROSIS; DNA-BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Zennaro, MC Univ Paris 07, INSERM, U478, BP 416,16 Rue Henri Huchard, F-75870 Paris 18, France Univ Paris 07 BP 416,16 Rue Henri Huchard Paris France 18 nce
Citazione:
M.C. Zennaro et al., "A new human MR splice variant is a ligand-independent transactivator modulating corticosteroid action", MOL ENDOCR, 15(9), 2001, pp. 1586-1598

Abstract

Aldosterone effects are mediated by the MR, which possesses the same affinity for mineralocorticoids and glucocorticoids. In addition to the existence of mechanisms regulating intracellular hormone availability, we searched for human MR splice variants involved in tissue-specific corticosteroid function. We have identified a new human MR isoform, hMR Delta5,6, resulting from an alternative splicing event skipping exons 5 and 6 of the human MR gene. hMR Delta5,6 mRNAs are expressed in several human tissues at different levels compared with wild-type human MR, as shown by real time PCR. Introduction of a premature stop codon results in a 75-kDa protein lacking the entire hinge region and ligand binding domain. Interestingly, hMR Delta5,6 is still capable of binding to DNA and acts as a ligand-independent transactivator, with maximal transcriptional induction corresponding to approximately30-40% of aldosterone-activated wild-type human MR. Coexpression of hMR Delta5,6 with human MR or human GR increases their transactivation potential at high doses of hormone. Finally, hMR Delta5,6 is able to recruit the coactivators, steroid receptor coactivator 1, receptor interacting protein 140,and transcription intermediary factor 1 a, which enhance its transcriptional activity. Ligand-independent transactivation and enhancement of both wild-type MR and GR activities by hMR Delta5,6 suggests that this new variant might play a role in modulating corticosteroid effects in target tissues.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/05/18 alle ore 12:55:57