期刊
JOURNAL OF CELL SCIENCE
卷 124, 期 20, 页码 3492-3502出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.088799
关键词
Neural differentiation; RAR alpha; Retinoic acid; TRIM32; Ubiquitin
类别
资金
- KAKENHI from Ministry of Education, Culture, Sports, Science and Technology [18076001, 21390087]
- Research Foundation Ituu Laboratory
- Grants-in-Aid for Scientific Research [18076001, 22390314, 21390087, 23659144] Funding Source: KAKEN
Retinoic acid (RA), a metabolite of vitamin A, plays versatile roles in development, differentiation, cell cycles and regulation of apoptosis by regulating gene transcription through nuclear receptor activation. Ubiquitinylation, which is one of the post-translational modifications, appears to be involved in the transcriptional activity of intranuclear receptors including retinoic acid receptor alpha (RAR alpha). Mutations in the tripartite motif-containing protein 32 gene (TRIM32; also known as E3 ubiquitin-protein ligase) have been reported to be responsible for limb-girdle muscular dystrophy type 2H in humans, and its encoded protein has been shown to interact with several other important proteins. In this study, we found that TRIM32 interacts with RAR alpha and enhances its transcriptional activity in the presence of RA. We also found that overexpression of TRIM32 in mouse neuroblastoma cells and embryonal carcinoma cells promoted stability of RAR alpha, resulting in enhancement of neural differentiation. These findings suggest that TRIM32 functions as one of the co-activators for RAR alpha-mediated transcription, and thereby TRIM32 is a potential therapeutic target for developmental disorders and RA-dependent leukemias.
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