Reversal of hyperactive Wnt signaling-dependent adipocyte defects by peptide boronic acids.
Proc Natl Acad Sci U S A
; 114(36): E7469-E7478, 2017 09 05.
Article
em En
| MEDLINE
| ID: mdl-28827348
ABSTRACT
Deregulated Wnt signaling and altered lipid metabolism have been linked to obesity, diabetes, and various cancers, highlighting the importance of identifying inhibitors that can modulate Wnt signaling and aberrant lipid metabolism. We have established a Drosophila model with hyperactivated Wnt signaling caused by partial loss of axin, a key component of the Wnt cascade. The Axin mutant larvae are transparent and have severe adipocyte defects caused by up-regulation of ß-catenin transcriptional activities. We demonstrate pharmacologic mitigation of these phenotypes in Axin mutants by identifying bortezomib and additional peptide boronic acids. We show that the suppressive effect of peptide boronic acids on hyperactive Wnt signaling is dependent on α-catenin; the rescue effect is completely abolished with the depletion of α-catenin in adipocytes. These results indicate that rather than targeting the canonical Wnt signaling pathway directly, pharmacologic modulation of ß-catenin activity through α-catenin is a potentially attractive approach to attenuating Wnt signaling in vivo.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Ácidos Borônicos
/
Adipócitos
/
Proteínas Wnt
/
Via de Sinalização Wnt
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article