Ajuba functions as a co-activator of C/EBPß to induce expression of PPARγ and C/EBPα during adipogenesis.
Mol Cell Endocrinol
; 539: 111485, 2022 01 01.
Article
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| MEDLINE
| ID: mdl-34619292
ABSTRACT
Adipogenesis is regulated by a complicated network of transcription factors among which PPARγ and C/EBP family members are the major regulators. During adipogenesis, C/EBPß is induced early and then transactivates PPARγ and C/EBPα, which cooperatively induce genes whose expressions give rise to the mature adipocyte phenotype. Identifying the factors that influence the expression and activity of C/EBPß should provide additional insight into the mechanisms regulating adipogenesis. Here, we demonstrate that depletion of Ajuba in 3T3-L1 cells significantly decreases mRNA and protein levels of PPARγ and C/EBPα and impairs adipocyte differentiation, while overexpression increases expression of these genes and promotes adipocyte differentiation. Moreover, restoration of C/EBPα or PPARγ expression in Ajuba-deficient 3T3-L1 cells improves the impaired lipid accumulation. Mechanistically, Ajuba interacts with C/EBPß and recruits CBP to facilitate the binding of C/EBPß to the promoter of PPARγ and C/EBPα, resulting in increased H3 histone acetylation and target gene expression. Collectively, these data indicate that Ajuba functions as a co-activator of C/EBPß, and may be an important therapeutic target for combating obesity-related diseases.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteína alfa Potenciadora de Unión a CCAAT
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Proteína beta Potenciadora de Unión a CCAAT
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PPAR gamma
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Proteínas con Dominio LIM
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Mol Cell Endocrinol
Año:
2022
Tipo del documento:
Article