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[摘要]：Ubiquitination, one of the posttranslational modifications, appears to be involved in the transcriptional activity of nuclear receptors including retinoic acid receptor alpha (RAR alpha). We previously reported that an E3 ubiquitin ligase, TRIM32, interacts with several important proteins including RAR alpha and enhances transcriptional activity of RAR alpha in mouse neuroblastoma cells and embryonal carcinoma cells. Retinoic acid (RA), which acts as a ligand to nuclear receptors including RAR alpha, plays crucial roles in development, differentiation, cell cycles and apoptosis. In this study, we found that TRIM32 enhances RAR alpha-mediated transcriptional activity even in the absence of RA and stabilizes RAR alpha 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 RAR alpha-mediated transcription in acute promyelogenous leukemia (APL) cells, and thus TRIM32 may become a potentially therapeutic target for APL (C) 2011 Elsevier Inc. All rights reserved. |
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