RGD Reference Report - Regulation of insulin secretion and beta-cell mass by activating signal cointegrator 2. - Rat Genome Database
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Regulation of insulin secretion and beta-cell mass by activating signal cointegrator 2.

Authors: Yeom, SY  Kim, GH  Kim, CH  Jung, HD  Kim, SY  Park, JY  Pak, YK  Rhee, DK  Kuang, SQ  Xu, J  Han, DJ  Song, DK  Lee, JW  Lee, KU  Kim, SW 
Citation: Yeom SY, etal., Mol Cell Biol. 2006 Jun;26(12):4553-63.
RGD ID: 9590126
Pubmed: (View Article at PubMed) PMID:16738321
DOI: Full-text: DOI:10.1128/MCB.01412-05

Activating signal cointegrator 2 (ASC-2) is a transcriptional coactivator of many nuclear receptors (NRs) and other transcription factors and contains two NR-interacting LXXLL motifs (NR boxes). In the pancreas, ASC-2 is expressed only in the endocrine cells of the islets of Langerhans, but not in the exocrine cells. Thus, we examined the potential role of ASC-2 in insulin secretion from pancreatic beta-cells. Overexpressed ASC-2 increased glucose-elicited insulin secretion, whereas insulin secretion was decreased in islets from ASC-2+/- mice. DN1 and DN2 are two dominant-negative fragments of ASC-2 that contain NR boxes 1 and 2, respectively, and block the interactions of cognate NRs with the endogenous ASC-2. Primary rat islets ectopically expressing DN1 or DN2 exhibited decreased insulin secretion. Furthermore, relative to the wild type, ASC-2+/- mice showed reduced islet mass and number, which correlated with increased apoptosis and decreased proliferation of ASC-2+/- islets. These results suggest that ASC-2 regulates insulin secretion and beta-cell survival and that the regulatory role of ASC-2 in insulin secretion appears to involve, at least in part, its interaction with NRs via its two NR boxes.

Annotation

Disease Annotations    

Gene Ontology Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Ncoa6  (nuclear receptor coactivator 6)

Genes (Mus musculus)
Ncoa6  (nuclear receptor coactivator 6)

Genes (Homo sapiens)
NCOA6  (nuclear receptor coactivator 6)


Additional Information