title: TRIM32 promotes neural differentiation through retinoic acid receptor-mediated transcription.
abstract: 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 α (RARα). 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 RARα 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 RARα, resulting in enhancement of neural differentiation. These findings suggest that TRIM32 functions as one of the co-activators for RARα-mediated transcription, and thereby TRIM32 is a potential therapeutic target for developmental disorders and RA-dependent leukemias.
authors: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638,  Japan.
authors: Tomonobu
authors: T
authors: Sato
authors: Fumihiko
authors: F
authors: Okumura
authors: Satoshi
authors: S
authors: Kano
authors: Takeshi
authors: T
authors: Kondo
authors: Tadashi
authors: T
authors: Ariga
authors: Shigetsugu
authors: S
authors: Hatakeyama
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D014411:Neoplastic Stem Cells; D009474:Neurons / Q000502:physiology*; D055550:Protein Stability; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D019076:Transgenes / Q000235:genetics; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000235:genetics
chemical_list: C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C094027:TRIM32 protein, human; D044767:Ubiquitin-Protein Ligases