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Non-DNA binding, dominant-negative, human PPAR gamma mutations cause lipodystrophic insulin resistance
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(2006) Non-DNA binding, dominant-negative, human PPAR gamma mutations cause lipodystrophic insulin resistance. Cell Metabolism, Volume 4 (Number 4). pp. 303-311. doi:10.1016/j.cmet.2006.09.003 ISSN 1550-4131.
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Official URL: http://dx.doi.org/10.1016/j.cmet.2006.09.003
Abstract
PPAR gamma is essential for adipogenesis and metabolic homeostasis. We describe mutations in the DNA and ligand binding domains of human PPAR gamma in lipodystrophic, severe insulin resistance. These receptor mutants lack DNA binding and transcriptional activity but can translocate to the nucleus, interact with PPAR gamma coactivators and inhibit coexpressed wild-type receptor. Expression of PPAR gamma target genes is markedly attenuated in mutation-containing versus receptor haploinsufficent primary cells, indicating that such dominant-negative inhibition operates in vivo. Our observations suggest that these mutants restrict wild-type PPAR gamma action via a non-DNA binding, transcriptional interference mechanism, which may involve sequestration of functionally limiting coactivators.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QH Natural history > QH301 Biology R Medicine > RC Internal medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | Cell Metabolism | ||||
Publisher: | Cell Press | ||||
ISSN: | 1550-4131 | ||||
Official Date: | October 2006 | ||||
Dates: |
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Volume: | Volume 4 | ||||
Number: | Number 4 | ||||
Number of Pages: | 9 | ||||
Page Range: | pp. 303-311 | ||||
DOI: | 10.1016/j.cmet.2006.09.003 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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