title: TRIM32 promotes retinoic acid receptor α-mediated differentiation in human promyelogenous leukemic cell line HL60.
abstract: Ubiquitination, one of the posttranslational modifications, appears to be involved in the transcriptional activity of nuclear receptors including retinoic acid receptor α (RARα). We previously reported that an E3 ubiquitin ligase, TRIM32, interacts with several important proteins including RARα and enhances transcriptional activity of RARα in mouse neuroblastoma cells and embryonal carcinoma cells. Retinoic acid (RA), which acts as a ligand to nuclear receptors including RARα, plays crucial roles in development, differentiation, cell cycles and apoptosis. In this study, we found that TRIM32 enhances RARα-mediated transcriptional activity even in the absence of RA and stabilizes RARα in the human promyelogenous leukemic cell line HL60. Moreover, we found that overexpression of TRIM32 in HL60 cells suppresses cellular proliferation and induces granulocytic differentiation even in the absence of RA. These findings suggest that TRIM32 functions as one of the coactivators for RARα-mediated transcription in acute promyelogenous leukemia (APL) cells, and thus TRIM32 may become a potentially therapeutic target for APL.
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Sato
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Okumura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Iguchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D039481:CD11b Antigen; C509295:ITGAM protein, human; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D014212:Tretinoin; C094027:TRIM32 protein, human; D044767:Ubiquitin-Protein Ligases