Cloning of the Novel Human Myeloid-Cell-Specific C/EBP-ε Transcription Factor

Chumakov, Alexey M.; Grillier, I; Chumakova, E. A.; Chih, Doris Y.; Slater, Jacquelyn S.; Koeffler, H. Phillip

doi:10.1128/mcb.17.3.1375

Cited by 130 publications

(125 citation statements)

References 83 publications

(98 reference statements)

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“…The rat C/EBP⑀ promoter contains potential C/EBP-binding sites at Ϫ157 and Ϫ454, and the human gene contains a near-perfect C/EBP consensus 324 bp upstream of the initiation site of the more highly used P␤ promoter. 43,52 Future experiments will determine whether C/EBP␣ or C/EBP␤ activates the C/EBP⑀ gene via these or other binding sites.…”

Section: Discussionmentioning

confidence: 99%

CCAAT/enhancer-binding proteins are required for granulopoiesis independent of their induction of the granulocyte colony-stimulating factor receptor

Wang

Friedman

2002

Blood

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Section: Discussionmentioning

confidence: 99%

CCAAT/enhancer-binding proteins are required for granulopoiesis independent of their induction of the granulocyte colony-stimulating factor receptor

Wang

Friedman

2002

Blood

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“…13 The CCAAT enhancer-binding protein-e (C/EBPe) is a family of transcription factors that regulates proliferation and differentiation of numerous cell types including granulocytes. 14,15 We and others previously showed that C/EBPe is pivotal to granulocytic differentiation. 16,17 C/EBPe modulates the levels of various cellcycle regulating molecules during differentiation; overexpression of C/EBPe downregulated the levels of c-Myc and upregulated the levels of cyclin-dependent kinase inhibitor p27 kip1 in myeloid cells.…”

Section: Introductionmentioning

confidence: 99%

Blockade of mTOR signaling potentiates the ability of histone deacetylase inhibitor to induce growth arrest and differentiation of acute myelogenous leukemia cells

et al. 2008

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This study found that MS-275, a novel synthetic benzamide histone deacetylase inhibitor (HDACI), blocked Akt/mammalian target of rapamycin (mTOR) signaling in acute myelogenous leukemia (AML) HL60 and acute promyelocytic leukemia (APL) NB4 cells, as assessed by decreased levels of the phosphorylated (p)-Akt, p-p70 ribosomal S6 kinase (p70S6K) and p-S6K by western blot analysis. Interestingly, further inactivation of mTOR by rapamycin analog RAD001 (everolimus) significantly enhanced MS-275-mediated growth inhibition and apoptosis of these cells in parallel with enhanced upregulation of p27 kip1 and downregulation of c-Myc. In addition, RAD001 potentiated the ability of MS-275 to induce differentiation of HL60 and NB4 cells, as measured by the expression of CD11b cell surface antigens, as well as reduction of nitroblue tetrazolium. Importantly, RAD001 potentiated the ability of MS-275 to induce the expression of the myeloid differentiation-related transcription factor, CCAAT enhancer-binding protein-e, in these cells in association with enhanced acetylation of histone H3 on its promoter. Furthermore, RAD001 (5 mg/kg) significantly enhanced the effects of MS-275 (10 mg/kg) to inhibit proliferation of HL60 tumor xenografts in nude mice without adverse effects. Taken together, concomitant administration of an HDACI and an mTOR inhibitor may be a promising treatment strategy for the individuals with a subset of human leukemia.

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“…1,2 Mice with a targeted disruption of the C/EBP⑀ locus lack mature granulocytes. The most differentiated C/EBP⑀ −/− granulocytic cells are dysplastic and not fully functional.…”

Section: Introductionmentioning

confidence: 99%

C/EBPε −/− mice: increased rate of myeloid proliferation and apoptosis

et al. 2001

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CCAAT/enhancer binding protein epsilon (C/EBP⑀) is essential for terminal granulocytic differentiation. Its expression begins at the transition between the proliferative and non-proliferative compartments of myelopoiesis. We studied the effect of targeted disruption of the C/EBP⑀ gene on murine myeloid proliferation and apoptosis. Bone marrow cellularity of C/EBP⑀ −/− and wild-type mice was 95% and 65%, respectively. The C/EBP⑀ −/− mice had an expansion in the number of their CFU-GM/femur. The number of myeloid committed progenitor cells in the peripheral blood and the spleen of these mice was also increased. Bromodeoxyuridine (BrDU) pulse labeling studies demonstrated that the fraction of actively proliferating cells was two-fold higher in the bone marrow of C/EBP⑀ −/− mice. However, the number of myeloid colonies arising from purified Sca-1+/lin− early hematopoietic progenitor cells and from bone marrow mononuclear cells grown in different cytokine combinations was not significantly different between wild-type and knock-out mice. Also, long-term marrow growth, and CFU were not different between the wild-type and C/EBP⑀ −/− mice. The sensitivity to induction of apoptosis in the committed progenitor cell compartment after either withdrawal of growth factor or brief exposure to etoposide was normal. However, Gr-1 antigen-positive C/EBP⑀ −/− granulocytic cells showed an increased rate of apoptosis in comparison to their wild-type counterparts. In summary, the myeloid compartment appears to be expanded in mice lacking C/EBP⑀. However, this is not the consequence of an intrinsic myeloproliferation but due to an indirect, possibly cytokine-mediated stimulation of myelopoiesis in vivo. C/EBP⑀ may have a role in the inhibition of apoptosis in maturing granulocytic cells. Leukemia (2001) 15, 103-111.

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Cloning of the Novel Human Myeloid-Cell-Specific C/EBP-ε Transcription Factor

Cited by 130 publications

References 83 publications

CCAAT/enhancer-binding proteins are required for granulopoiesis independent of their induction of the granulocyte colony-stimulating factor receptor

CCAAT/enhancer-binding proteins are required for granulopoiesis independent of their induction of the granulocyte colony-stimulating factor receptor

Blockade of mTOR signaling potentiates the ability of histone deacetylase inhibitor to induce growth arrest and differentiation of acute myelogenous leukemia cells

C/EBPε −/− mice: increased rate of myeloid proliferation and apoptosis

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