Upregulation of SIRT1 by 17β-estradiol depends on ubiquitin-proteasome degradation of PPAR-γ mediated by NEDD4-1
Protein & Cell
;
(12): 310-321, 2013.
Article
Dans Anglais
| WPRIM
| ID: wpr-757809
ABSTRACT
17β-estradiol (E2) treatment of cells results in an upregulation of SIRT1 and a down-regulation of PPARγ. The decrease in PPARγ expression is mediated by increased degradation of PPARγ. Here we report that PPARγ is ubiquitinated by HECT E3 ubiquitin ligase NEDD4-1 and degraded, along with PPARγ, in response to E2 stimulation. The PPARγ interacts with ubiquitin ligase NEDD4-1 through a conserved PPXY-WW binding motif. The WW3 domain in NEDD4-1 is critical for binding to PPARΓ. NEDD4-1 overexpression leads to PPARγ ubiquitination and reduced expression of PPARγ. Conversely, knockdown of NEDD4-1 by specific siRNAs abolishes PPARΓ ubiquitination. These data indicate that NEDD4-1 is the E3 ubiquitin ligase responsible for PPARγ ubiquitination. Here, we show that NEDD4-1 delays cellular senescence by degrading PPARΓ expression. Taken together, our data show that E2 could upregulate SIRT1 expression via promoting the PPARΓ ubiquitination-proteasome degradation pathway to delay the process of cell senescence.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Pharmacologie
/
Cellules HeLa
/
Régulation négative
/
Régulation positive
/
Vieillissement de la cellule
/
Structure tertiaire des protéines
/
Motifs d'acides aminés
/
Ubiquitine
/
Petit ARN interférent
/
Interférence par ARN
Limites du sujet:
Animaux
/
Femelle
/
Humains
langue:
Anglais
Texte intégral:
Protein & Cell
Année:
2013
Type:
Article
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