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ID 117429
Title Alternative
全トランスレチノイン酸はMAPKシグナル依存的なGADD34の増加を介して筋繊維タイプを変化させる
Increase of GADD34 expression in skeletal muscle by ATRA
Author
Adachi, Yuichiro Tokushima University
Niida, Yuki Tokushima University
Mori, Yuki Tokushima University
Okumura, Yosuke Tokushima University
Ohnishi, Kohta Tokushima University
Keywords
MAPK
mRNA stabilization
skeletal muscle type change
transcription
unfolded protein response
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Life Science Alliance
ISSN
25751077
Publisher
Life Science Alliance
Volume
5
Issue
7
Start Page
e202101345
Published Date
2022-03-22
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Yuichiro Adachiの学位論文として提出され,学位審査・授与の対象となっている。
Rights
This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3707号
Diploma Number
甲栄第295号
Granted Date
2023-03-23
Degree Name
Doctor of Nutritional Science
Grantor
Tokushima University
departments
Medical Sciences