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Conference Paper: Down-regulation of the human secretin gene expression by an atypical nuclear orphan receptor, small heterodimer partner (SHP)

TitleDown-regulation of the human secretin gene expression by an atypical nuclear orphan receptor, small heterodimer partner (SHP)
Authors
Issue Date2005
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/regpep
Citation
The 7th International Symposium on VIP, PACAP and Related Peptides, Rouen, France, 11-14 September 2005. In Regulatory Peptides, 2005, v. 130 n. 3, p. 167 How to Cite?
AbstractSmall Heterodimer Partner (SHP) is an orphan nuclear receptor that lacks a DNA-binding domain (DBD). SHP transcription can be enhanced by several nuclear receptors, including farnesoid X receptor (FXR). It has been demonstrated that, FXR is activated by bile acids. Therefore, bile acid can up-regulate SHP expression through FXR. On the other hand, SHP represses the transcriptional activities of NeuroD via physical contacts and displacing the coactivator p300. The transcription of secretin gene is partly driven by the NeuroD and E2A (E47 and E12) heterodimer interacting with the E-box motif, which is potentiated by p300 binding. In view of this, NeuroD-dependent secretin transcription can potentially be regulated by SHP. Furthermore, SHP may confer a novel pathway for secretin transcription in response to bile acids. In regard to the hypothesis, the regulatory role of SHP in human secretin gene expression was confirmed by over-expression of SHP in HuTu-80 cells, which led to dose-dependent decreases of both secretin promoter activities and endogenous secretin transcript levels. In contrast, silencing of endogenous SHP by the siRNA sequences, siRNA-1 and siRNA-2, augmented secretin promoter activity. On top of SHP, our studies have also demonstrated that the bile acid, CDCA, could effectively raise endogenous SHP transcript levels and down-regulate the secretin promoter. These results suggest that binding of CDCA to FXR activates SHP expression which eventually leads to down-regulation of secretin. In summary, the proposed hypothesis provides a negative regulatory loop that the secretin-stimulated bile acids, via SHP, can down-regulate secretin expression to reduce the long-term bile flow.
Descriptionpp. 133-188 of this journal issue entitled: Abstracts of the 7th International Symposium on VIP, PACAP and Related Peptides. Rouen, France. September 11-14, 2005
Persistent Identifierhttp://hdl.handle.net/10722/110626
ISSN
2015 Impact Factor: 1.813
2015 SCImago Journal Rankings: 0.915

 

DC FieldValueLanguage
dc.contributor.authorLam, PYen_HK
dc.contributor.authorLee, TOen_HK
dc.contributor.authorChow, BKCen_HK
dc.date.accessioned2010-09-26T02:14:00Z-
dc.date.available2010-09-26T02:14:00Z-
dc.date.issued2005en_HK
dc.identifier.citationThe 7th International Symposium on VIP, PACAP and Related Peptides, Rouen, France, 11-14 September 2005. In Regulatory Peptides, 2005, v. 130 n. 3, p. 167-
dc.identifier.issn0167-0115-
dc.identifier.urihttp://hdl.handle.net/10722/110626-
dc.descriptionpp. 133-188 of this journal issue entitled: Abstracts of the 7th International Symposium on VIP, PACAP and Related Peptides. Rouen, France. September 11-14, 2005-
dc.description.abstractSmall Heterodimer Partner (SHP) is an orphan nuclear receptor that lacks a DNA-binding domain (DBD). SHP transcription can be enhanced by several nuclear receptors, including farnesoid X receptor (FXR). It has been demonstrated that, FXR is activated by bile acids. Therefore, bile acid can up-regulate SHP expression through FXR. On the other hand, SHP represses the transcriptional activities of NeuroD via physical contacts and displacing the coactivator p300. The transcription of secretin gene is partly driven by the NeuroD and E2A (E47 and E12) heterodimer interacting with the E-box motif, which is potentiated by p300 binding. In view of this, NeuroD-dependent secretin transcription can potentially be regulated by SHP. Furthermore, SHP may confer a novel pathway for secretin transcription in response to bile acids. In regard to the hypothesis, the regulatory role of SHP in human secretin gene expression was confirmed by over-expression of SHP in HuTu-80 cells, which led to dose-dependent decreases of both secretin promoter activities and endogenous secretin transcript levels. In contrast, silencing of endogenous SHP by the siRNA sequences, siRNA-1 and siRNA-2, augmented secretin promoter activity. On top of SHP, our studies have also demonstrated that the bile acid, CDCA, could effectively raise endogenous SHP transcript levels and down-regulate the secretin promoter. These results suggest that binding of CDCA to FXR activates SHP expression which eventually leads to down-regulation of secretin. In summary, the proposed hypothesis provides a negative regulatory loop that the secretin-stimulated bile acids, via SHP, can down-regulate secretin expression to reduce the long-term bile flow.-
dc.languageengen_HK
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/regpep-
dc.relation.ispartofRegulatory Peptidesen_HK
dc.rightsRegulatory Peptides. Copyright © Elsevier BV.-
dc.titleDown-regulation of the human secretin gene expression by an atypical nuclear orphan receptor, small heterodimer partner (SHP)en_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLee, TO: ltolee2@hkucc.hku.hken_HK
dc.identifier.emailChow, BKC: bkcc@hkusua.hku.hken_HK
dc.identifier.authorityLee, TO=rp00727en_HK
dc.identifier.authorityChow, BKC=rp00681en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.regpep.2005.06.011-
dc.identifier.hkuros103380en_HK
dc.identifier.hkuros123490-
dc.identifier.hkuros157555-
dc.identifier.volume130-
dc.identifier.issue3-
dc.identifier.spage167-
dc.identifier.epage167-

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