All-trans retinoic acid changes muscle fiber type via increasing GADD34 dependent on MAPK signal.
Life Sci Alliance
; 5(7)2022 03.
Article
en En
| MEDLINE
| ID: mdl-35318262
ABSTRACT
All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response in differentiating leukemic blasts. The downstream transcriptional factor of PERK, a major arm of unfolded protein response, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of GADD34 gene via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the GADD34 gene promoter in skeletal muscle. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on GADD34 mRNA via p-38 MAPK, resulting in the instability of GADD34 mRNA. Overexpressed GADD34 in C2C12 cells changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation, which changes muscle fiber type.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tretinoina
/
Fibras Musculares Esqueléticas
/
Proteína Fosfatasa 1
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Life Sci Alliance
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón