Promyelocytic leukemia protein (PML) functions as a glucocorticoid receptor co-activator by sequestering Daxx to the PML oncogenic domains (PODs) to enhance its transactivation potential

Ding Yen Lin, Ming Zong Lai, David K. Ann, Hsiu Ming Shih

研究成果: Article同行評審

68 引文 斯高帕斯(Scopus)

摘要

Daxx has been reported to function as a transcriptional modulator in the nucleus. In the present study, we have explored the role of Daxx in regulating the transcriptional activity of the glucocorticoid receptor (GR). Overexpression of Daxx suppressed GR-mediated activation of the mouse mammary tumor virus promoter in COS-1, HeLa, and 293T cells. In vitro and in vivo studies revealed that Daxx could directly bind to GR. The mapping analysis further demonstrated that the C-terminal region of Daxx-(501-740) mediates the interaction and transcriptional repression of GR. The repressive effect of Daxx and Daxx-(501-740) on GR could be alleviated by co-expression of promyelocytic leukemia protein (PML). Furthermore, immunofluorescence analysis showed that overexpression of wild-type PML results in the translocation of Daxx and Daxx-(501-740) to the PML oncogenic domains (PODs). By contrast, a PML PA sumoylation-defective mutant failed to recruit Daxx to PODs and to reverse the Daxx repression effect on GR. Accordingly, AS2O3 treatment rendered the sequestration of endogenous Daxx to the PODs, leading to an enhancement of GR transactivation in COS-1 cells. Taken together, these findings suggest that recruitment of Daxx into the subnuclear POD structures sequesters it from the GR/co-activators complex, thereby alleviating its repressive effects. Our present studies provide the important link between Daxx/PML interaction and GR transcriptional activation.

原文English
頁(從 - 到)15958-15965
頁數8
期刊Journal of Biological Chemistry
278
發行號18
DOIs
出版狀態Published - 2003 5月 2

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 分子生物學
  • 細胞生物學

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