Spermidine promotes adipogenesis of 3T3-L1 cells by preventing interaction of ANP32 with HuR and PP2A.
Biochem J
; 453(3): 467-74, 2013 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-23672317
ABSTRACT
We have shown previously that the polyamine spermidine is indispensable for differentiation of 3T3-L1 preadipocytes. In the present study, we examined the mechanism of spermidine function by using the polyamine biosynthesis inhibitor α-difluoromethylornithine in combination with the metabolically stable polyamine analogues γ-methylspermidine or (R,R)-α,ω-bismethylspermine. At the early phase of differentiation, spermidine-depleted 3T3-L1 cells showed decreased translation of the transcription factor C/EBPß (CCAAT/enhancer-binding protein ß), decreased PP2A (protein phosphatase 2A) activity and increased cytoplasmic localization of the RNA-binding protein HuR (human antigen R). The amount of HuR bound to C/EBPß mRNA was reduced, whereas the amount of bound CUGBP2, an inhibitor of C/EBPß translation, was increased. ANP32 (acidic nuclear phosphoprotein 32) proteins, which are known PP2A inhibitors and HuR ligands, bound more PP2A and HuR in spermidine-depleted than in control cells, whereas immunodepletion of ANP32 proteins from the lysate of spermidine-depleted cells restored PP2A activity. Taken together, our data shows that spermidine promotes C/EBPß translation in differentiating 3T3-L1 cells, and that this process is controlled by the interaction of ANP32 with HuR and PP2A.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Espermidina
/
Proteínas ELAV
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Adipogenia
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Proteína Fosfatase 2
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article