SET8 is a novel negative regulator of TGF-ß signaling in a methylation-independent manner.
Sci Rep
; 13(1): 22877, 2023 12 18.
Article
en En
| MEDLINE
| ID: mdl-38129484
ABSTRACT
Transforming growth factor ß (TGF-ß) is a multifunctional cytokine that induces a diverse set of cellular processes principally through Smad-dependent transcription. Transcriptional responses induced by Smads are tightly regulated by Smad cofactors and histone modifications; however, the underlying mechanisms have not yet been elucidated in detail. We herein report lysine methyltransferase SET8 as a negative regulator of TGF-ß signaling. SET8 physically associates with Smad2/3 and negatively affects transcriptional activation by TGF-ß in a catalytic activity-independent manner. The depletion of SET8 results in an increase in TGF-ß-induced plasminogen activator inhibitor-1 (PAI-1) and p21 expression and enhances the antiproliferative effects of TGF-ß. Mechanistically, SET8 occupies the PAI-1 and p21 promoters, and a treatment with TGF-ß triggers the replacement of the suppressive binding of SET8 with p300 on these promoters, possibly to promote gene transcription. Collectively, the present results reveal a novel role for SET8 in the negative regulation of TGF-ß signaling.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Factor de Crecimiento Transformador beta
/
Inhibidor 1 de Activador Plasminogénico
Idioma:
En
Revista:
Sci Rep
Año:
2023
Tipo del documento:
Article
País de afiliación:
Japón