PML-retinoic acid receptor α inhibits PML IV enhancement of PU.1-induced C/EBPε expression in myeloid differentiation Journal Article
| Authors: | Yoshida, H.; Ichikawa, H.; Tagata, Y.; Katsumoto, T.; Ohnishi, K.; Akao, Y.; Naoe, T.; Pandolfi, P. P.; Kitabayashi, I. |
| Article Title: | PML-retinoic acid receptor α inhibits PML IV enhancement of PU.1-induced C/EBPε expression in myeloid differentiation |
| Abstract: | PML and PU.1 play important roles in myeloid differentiation. PML-deficient mice have an impaired capacity for terminal maturation of their myeloid precursor cells. This finding has been explained, at least in part, by the lack of PML action to modulate retinoic acid-differentiating activities. In this study, we found that C/EBPε expression is reduced in PML-deflcient mice. We showed that PU.1 directly activates the transcription of the C/EBPε gene that is essential for granulocytic differentiation. The type IV isoform of PML interacted with PU.1, promoted its association with p300, and then enhanced PU.1-induced transcription and granulocytic differentiation. In contrast to PML IV, the leukemia-associated PML-retinoic acid receptor α fusion protein dissociated the PU.1/PML IV/p300 complex and inhibited PU.1-induced transcription. These results suggest a novel pathogenic mechanism of the PML-retinoic acid receptor α fusion protein in acute promyelocyte leukemia. Copyright © 2007, American Society for Microbiology. All Rights Reserved. |
| Keywords: | controlled study; protein expression; leukemia; unclassified drug; human cell; proto-oncogene proteins; nonhuman; animal cell; mouse; animals; mice; mus; complex formation; cell maturation; protein protein interaction; neoplasm proteins; protein binding; genetic transcription; cell differentiation; transcription, genetic; hela cells; structure activity relation; structure-activity relationship; transcription factors; nuclear proteins; molecular sequence data; tumor suppressor proteins; promyelocytic leukemia; oncogene proteins, fusion; base sequence; trans-activators; bone marrow cell; retinoic acid; protein isoforms; nih 3t3 cells; granulocyte; ccaat-enhancer-binding proteins; promyelocytic leukemia protein; retinoic acid receptor alpha; myeloid cells; protein p300; myelopoiesis; e1a-associated p300 protein; transcription factor pu 1; ccaat enhancer binding protein; ccaat enhancer binding protein epsilon; granulopoiesis; granulocyte precursor cells |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 27 |
| Issue: | 16 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2007-08-01 |
| Start Page: | 5819 |
| End Page: | 5834 |
| Language: | English |
| DOI: | 10.1128/mcb.02422-06 |
| PUBMED: | 17562868 |
| PROVIDER: | scopus |
| PMCID: | PMC1952121 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 15" - "Export Date: 17 November 2011" - "CODEN: MCEBD" - "Source: Scopus" |
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