The acute promyelocytic leukemia-associated protein, promyelocytic leukemia zinc finger, regulates 1,25-dihydroxyvitamin D 3-induced monocytic differentiation of U937 cells through a physical interaction with vitamin D 3 receptor Journal Article
| Authors: | Ward, J. O.; McConnell, M. J.; Carlile, G. W.; Pandolfi, P. P.; Licht, J. D.; Freedman, L. P. |
| Article Title: | The acute promyelocytic leukemia-associated protein, promyelocytic leukemia zinc finger, regulates 1,25-dihydroxyvitamin D 3-induced monocytic differentiation of U937 cells through a physical interaction with vitamin D 3 receptor |
| Abstract: | Monocyte differentiation induced by 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3) is interrupted during the course of acute promyelocytic leukemia (APL). One form of APL is associated with the translocation t(11;17), which joins the promyelocytic leukemia zinc finger (PLZF) and retinoic acid receptor α (RARα) genes. Because PLZF is coexpressed in the myeloid lineage with the vitamin D 3 receptor (VDR), the interplay between PLZF and VDR was examined. It was found that PLZF interacts directly with VDR. This occurred at least partly through contacts in the DNA-binding domain of VDR and the broad complex, tram-trak, bric-a-brac/pox virus zinc finger (BTB/POZ) domain of PLZF. Moreover, PLZF altered the mobility of VDR derived from nuclear extracts when bound to its cognate binding site, forming a slowly migrating DNA-protein complex. Overexpression of PLZF in a monocytic cell line abrogated 1,25(OH) 2D 3 activation from both a minimal VDR responsive reporter and the promoter of p21 WAF1/CIP1, a target gene of VDR. Deletion of the BTB/POZ domain significantly relieved PLZF-mediated repression of 1,25(OH) 2D 3-dependent activation. In addition, stable, inducible expression of PLZF in U937 cells inhibited the ability of 1,25(OH) 2D 3 to induce surface expression of the monocytic marker CD14 and morphologic changes associated with differentiation. These results suggest that PLZF may play an important role in regulating the process by which 1,25(OH) 2D 3 induces monocytic differentiation in hematopoietic cells. © 2001 by The American Society of Hematology. |
| Keywords: | human cell; dna-binding proteins; flow cytometry; gene expression; genetic transcription; cell differentiation; transcription, genetic; calcitriol; transfection; transcription factors; dna; transcription regulation; hybrid protein; promyelocytic leukemia; hematopoietic cell; chromosome translocation; binding sites; cell nucleus; cyclin-dependent kinase inhibitor p21; monocytes; cyclins; vitamin d receptor; zinc finger protein; retinoic acid; cell strain u937; u937 cells; retinoic acid receptor; zinc fingers; dna protein complex; lymphoma cell line; promoter regions (genetics); receptors, calcitriol; lymphoma, large-cell; humans; human; priority journal; article; vitamin d responsive element |
| Journal Title: | Blood |
| Volume: | 98 |
| Issue: | 12 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2001-12-01 |
| Start Page: | 3290 |
| End Page: | 3300 |
| Language: | English |
| DOI: | 10.1182/blood.V98.12.3290 |
| PUBMED: | 11719366 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
