SIAH2 is Expressed in Adipocyte Precursor Cells and Interacts with EBF1 and ZFP521 to Promote Adipogenesis.
Obesity (Silver Spring)
; 29(1): 98-107, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-33155406
ABSTRACT
OBJECTIVE:
Expression of zinc finger protein 423 (ZFP423), a key proadipogenic transcription factor in adipocyte precursor cells, is regulated by interaction of the proadipogenic early B-cell factor 1 (EBF1) and antiadipogenic ZFP521. The ubiquitin ligase seven-in-absentia homolog 2 (SIAH2) targets ZFP521 for degradation. This study asked whether SIAH2 is expressed in adipocyte precursor cells and whether SIAH2 interacts with ZFP521 and EBF1 to regulate ZFP521 protein levels during adipogenesis.METHODS:
SIAH2 expression in precursor cells was assessed in primary cells and tissues from wild-type and SIAH2 null mice fed a control or high-fat diet. Primary cells, 3T3-L1 preadipocytes, and HEK293T cells were used to analyze Siah2, Ebf1, and Zfp521 expression and SIAH2-mediated changes in ZFP521 and EBF1 protein levels.RESULTS:
Siah2 is expressed in platelet-derived growth factor receptor α (PDGFRα)+ and stem cell antigen-1 (SCA1)+ adipocyte precursor cells. SIAH2 depletion reduces Ebf1 gene expression and increases EBF1 protein levels in early but not late adipogenesis. In early adipogenesis, SIAH2 forms a protein complex with EBF1 and ZFP521 to enhance SIAH2-mediated ubiquitylation and degradation of ZFP521 while increasing EBF1 protein levels.CONCLUSIONS:
Siah2 is expressed in PDGFRα+ adipocyte precursor cells and is linked to precursor cell commitment to adipogenesis by interacting with EBF1 and ZFP521 proteins to target the antiadipogenic ZFP521 for degradation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Transativadores
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Adipócitos
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Ubiquitina-Proteína Ligases
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Adipogenia
Limite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Obesity (Silver Spring)
Assunto da revista:
CIENCIAS DA NUTRICAO
/
FISIOLOGIA
/
METABOLISMO
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos