The myeloid zinc finger gene (MZF-1) delays retinoic acid-induced apoptosis and differentiation in myeloid leukemia cells

Robertson, Kent A.; Hill, David P.; Kelley, Mark R.; Tritt, Renee; Crum, B.; Epps, S. Van; Srour, Edward F.; Rice, Susan; Hromas, Robert

doi:10.1038/sj.leu.2401005

Cited by 45 publications

(31 citation statements)

References 19 publications

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“…Many of them are reported to be involved in the regulation of apoptosis and cellcycle progression, confirming the reported roles of MZF-1 in the regulation of cell differentiation and proliferation [34][35][36].…”

Section: Discussionsupporting

confidence: 64%

FHL3 negatively regulates human high-affinity IgE receptor β-chain gene expression by acting as a transcriptional co-repressor of MZF-1

Takahashi

Matsumoto

2005

Biochemical Journal

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The high-affinity IgE receptor FcεRI plays a key role in triggering allergic reactions. We recently reported that human FcεRI β-chain gene expression was down-regulated by a transcription factor, MZF-1, through an element in the fourth intron. In the present study, we found that this transcriptional repression by MZF-1 required FHL3 (four and a half LIM domain protein 3) as a cofactor. Yeast two-hybrid and immunoprecipitation assays demonstrated that FHL3 bound MZF-1 in vitro and in vivo. Overexpression of FHL3 in KU812 cells suppressed the β-chain promoter activity through the element in the fourth intron in an MZF-1-dependent manner. Furthermore, results from pull-down assays and gel-filtration chromatography employing nuclear extracts indicated that MZF-1 and FHL3 formed a complex of high molecular mass with some additional proteins in the nucleus. Granulocyte-macrophage colony-stimulating factor, which was reported to decrease FcεRI expression, induced the accumulation of FHL3 in the nucleus, in accordance with the repressive role of FHL3 in β-chain gene expression.

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Section: Discussionsupporting

confidence: 64%

FHL3 negatively regulates human high-affinity IgE receptor β-chain gene expression by acting as a transcriptional co-repressor of MZF-1

Takahashi

Matsumoto

2005

Biochemical Journal

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“…[27][28][29][30][31][32] Moreover, these findings show the potential of comprehensive promoter analysis to identify TFs that might serve as targets for therapeutic interventions.…”

Section: Discussionmentioning

confidence: 99%

“…25,26 In contrast, genes upregulated in APL cells versus PMs contained a significant enrichment of binding sites for TFs that are instrumental for malignant transformation in cell lines and AML (MZF1, ARNT), and most strikingly for proliferation, mobilization and self-renewal of HSCs and/or leukemic stem cells (LSCs) (ERG1, NFKB, NFKB1). [27][28][29][30][31][32] APL cells show a partial stemness signature Our promoter analysis revealed that genes upregulated in APL cells versus PMs were significantly enriched in binding sites for TFs that conduct HSC maintenance/self-renewal. This led us to the hypothesis that APL cells might differ form PMs by expression of genes associated with HSC maintenance/selfrenewal.…”

Section: Transcriptional Regime Of Genes Dysregulated In Aplmentioning

confidence: 99%

A conceptual framework for the identification of candidate drugs and drug targets in acute promyelocytic leukemia

et al. 2010

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Chromosomal translocations of transcription factors generating fusion proteins with aberrant transcriptional activity are common in acute leukemia. In acute promyelocytic leukemia (APL), the promyelocytic leukemia-retinoic-acid receptor alpha (PML-RARA) fusion protein, which emerges as a consequence of the t(15;17) translocation, acts as a transcriptional repressor that blocks neutrophil differentiation at the promyelocyte (PM) stage. In this study, we used publicly available microarray data sets and identified signatures of genes dysregulated in APL by comparison of gene expression profiles of APL cells and normal PMs representing the same stage of differentiation. We next subjected our identified APL signatures of dysregulated genes to a series of computational analyses leading to (i) the finding that APL cells show stem cell properties with respect to gene expression and transcriptional regulation, and (ii) the identification of candidate drugs and drug targets for therapeutic interventions. Significantly, our study provides a conceptual framework that can be applied to any subtype of AML and cancer in general to uncover novel information from published microarray data sets at low cost. In a broader perspective, our study provides strong evidence that genomic strategies might be used in a clinical setting to prospectively identify candidate drugs that subsequently are validated in vitro to define the most effective drug combination for individual cancer patients on a rational basis.

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“…In addition, because LDOC1 possesses an SH3-binding site, it is possible that Src kinase activated through a specific stimulation phosphorylates LDOC1 and enables it to bind MZF-1 and localize to the nucleus. Interestingly, MZF-1 itself was reported to inhibit apoptosis in several cell lines [18][19][20] and enhance the expression of Bcl-2 [18]. The apoptosis-inducing activity of LDOC1 may be partly due to inhibition of this anti-apoptotic effect of MZF-1.…”

Section: Discussionmentioning

confidence: 99%

LDOC1, a novel MZF‐1‐interacting protein, induces apoptosis

et al. 2004

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LDOC1 was isolated as a gene encoding a leucinezipper protein whose expression was decreased in pancreatic and gastric cancer cell lines in 1999. Here, we found that overexpression of LDOC1 caused externalization of the cell membrane phosphatidylserine, which was characteristic for early-phase apoptotic events, and reduced cell viability in some human cell lines. The apoptotic process was triggered by a loss of the mitochondrial membrane potential, leading to both caspase-3-dependent and -independent pathways. Furthermore, a transcription factor, MZF-1, was revealed to interact with LDOC1 and enhance the activity of LDOC1 for inducing apoptosis.

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The myeloid zinc finger gene (MZF-1) delays retinoic acid-induced apoptosis and differentiation in myeloid leukemia cells

Cited by 45 publications

References 19 publications

FHL3 negatively regulates human high-affinity IgE receptor β-chain gene expression by acting as a transcriptional co-repressor of MZF-1

FHL3 negatively regulates human high-affinity IgE receptor β-chain gene expression by acting as a transcriptional co-repressor of MZF-1

A conceptual framework for the identification of candidate drugs and drug targets in acute promyelocytic leukemia

LDOC1, a novel MZF‐1‐interacting protein, induces apoptosis

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