scholarly journals Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor, polyomavirus enhancer binding protein 2/core binding factor

1997 ◽  
Vol 94 (11) ◽  
pp. 5697-5702 ◽  
Author(s):  
M. Niki ◽  
H. Okada ◽  
H. Takano ◽  
J. Kuno ◽  
K. Tani ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Fetal Liver ◽  
Binding Protein ◽  
Targeted Mutagenesis ◽  
Core Binding Factor ◽  
Gene Encoding ◽  
Enhancer Binding Protein ◽  
Binding Factor ◽  
Binding Subunit

scholarly journals Cytoplasmic Sequestration of the Polyomavirus Enhancer Binding Protein 2 (PEBP2)/Core Binding Factor α (CBFα) Subunit by the Leukemia-Related PEBP2/CBFβ-SMMHC Fusion Protein Inhibits PEBP2/CBF-Mediated Transactivation

1998 ◽  
Vol 18 (7) ◽  
pp. 4252-4261 ◽  
Author(s):  
Yuka Kanno ◽  
Tomohiko Kanno ◽  
Chohei Sakakura ◽  
Suk-Chul Bae ◽  
Yoshiaki Ito
Keyword(s):  
Nuclear Translocation ◽  
Binding Protein ◽  
Myelogenous Leukemia ◽  
Luciferase Assay ◽  
Β Subunit ◽  
Core Binding Factor ◽  
Α Subunit ◽  
Enhancer Binding Protein ◽  
Binding Factor ◽  
Minimal Region

ABSTRACT The polyomavirus enhancer binding protein 2 (PEBP2)/core binding factor (CBF) is a transcription factor composed of two subunits, α and β. The gene encoding the β subunit is disrupted by inv(16), resulting in the formation of a chimeric protein, β-SMMHC, which is associated with acute myelogenous leukemia. To understand the effect of β-SMMHC on PEBP2-mediated transactivation, we used a luciferase assay system in which contribution of both the α and β subunits was absolutely required to activate transcription. Using this system, we found that the minimal region of the β subunit required for transactivation resides between amino acid 1 and 135, which is known to dimerize with the α subunit. In contrast, β-SMMHC, despite having this minimal region for dimerization and transactivation, failed to support transcription with the α subunit. Furthermore β-SMMHC blocked the synergistic transcription achieved by PEBP2 and CCAAT/enhancer binding protein α. By using a construct in which the PEBP2 α subunit was fused to the glucocorticoid receptor ligand binding domain, we demonstrated that coexpressed β-SMMHC tightly sequestered the α subunit in the cytoplasm and blocked dexamethasone-dependent nuclear translocation of the α subunit. Thus, the result suggess that β-SMMHC inhibits PEBP2-mediated transcription via cytoplasmic sequestration of the α subunit. Lastly proliferation of ME-1 cells that harbor inv(16) was blocked by an antisense oligonucleotide complementary to the junction of the chimeric mRNA, suggesting that β-SMMHC contributes to leukemogenesis by blocking the differentiation of myeloid cells.

Role of transcription factor CCAAT/enhancer-binding protein alpha in human fetal liver cell typesin vitro

2014 ◽  
Vol 45 (8) ◽  
pp. 919-932 ◽  
Author(s):  
Jörg C. Gerlach ◽  
Patrick Over ◽  
Hubert G. Foka ◽  
Morris E. Turner ◽  
Robert L. Thompson ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Liver Cell ◽  
Fetal Liver ◽  
Binding Protein ◽  
Human Fetal Liver ◽  
Fetal Liver Cell ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein

AML1-FOG2 Fusion Protein in Myelodysplasia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2900-2900
Author(s):  
Edward Chan ◽  
Elisha Comer ◽  
Frank Brown ◽  
Kathleen Richkind ◽  
Melissa Holmes ◽  
...  
Keyword(s):  
Dna Binding ◽  
Transcriptional Repression ◽  
Myeloid Leukemia ◽  
Gene Fusions ◽  
The Novel ◽  
Core Binding Factor ◽  
Hematopoietic Stem ◽  
Binding Factor ◽  
Partner Gene ◽  
Binding Subunit

Abstract Core binding factor (CBF) participates in specification of the hematopoietic stem cell and functions as a critical regulator of hematopoiesis. Translocation or point mutation of AML1, which encodes the DNA-binding subunit of CBF, plays a central role in the pathogenesis of acute myeloid leukemia and myelodysplasia. We characterized the translocation t(X;21)(p22.3;q22.1) in a patient with myelodysplasia that fuses AML1 to the novel partner gene Friend of GATA-2 (FOG2). The reciprocal gene fusions AML1-FOG2 and FOG2-AML1 are both expressed. AML1-FOG2, which fuses the DNA-binding domain of AML1 to most of FOG2, represses transcription from the promoter of a hematopoietic target of AML1. AML1-FOG2 retains a motif that recruits the corepressor C-terminal binding protein (CtBP) and both proteins associate in a protein complex. These results suggest a role for CtBP in AML1-FOG2 transcriptional repression and implicate coordinated disruption of the AML1 and GATA developmental programs in the pathogenesis of myelodysplasia.

scholarly journals Transcription Factor Activating Enhancer-binding Protein-2β

2006 ◽  
Vol 281 (42) ◽  
pp. 31245-31253
Author(s):  
Kazuhiro Ikeda ◽  
Hiroshi Maegawa ◽  
Satoshi Ugi ◽  
Yukari Tao ◽  
Yoshihiko Nishio ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Protein ◽  
Enhancer Binding Protein

scholarly journals Insight into the Dual Functions of Bacterial Enhancer-Binding Protein Rrp2 of Borrelia burgdorferi

2016 ◽  
Vol 198 (10) ◽  
pp. 1543-1552 ◽  
Author(s):  
Yanping Yin ◽  
Youyun Yang ◽  
Xuwu Xiang ◽  
Qian Wang ◽  
Zhang-Nv Yang ◽  
...  
Keyword(s):  
Dna Binding ◽  
Borrelia Burgdorferi ◽  
Binding Protein ◽  
Phosphorylation Site ◽  
Binding Motif ◽  
Cell Replication ◽  
Additional Function ◽  
Content Type ◽  
Terminal Domain ◽  
Enhancer Binding Protein

ABSTRACTIt is well established that the RpoN-RpoS sigma factor (σ54-σS) cascade plays an essential role in differential gene expression during the enzootic cycle ofBorrelia burgdorferi, the causative agent of Lyme disease. The RpoN-RpoS pathway is activated by the response regulator/σ54-dependent activator (also called bacterial enhancer-binding protein [bEBP]) Rrp2. One unique feature of Rrp2 is that this activator is essential for cell replication, whereas RpoN-RpoS is dispensable for bacterial growth. How Rrp2 controls cell replication, a function that is independent of RpoN-RpoS, remains to be elucidated. In this study, by generating a series of conditionalrrp2mutant strains, we demonstrated that the N-terminal receiver domain of Rrp2 is required for spirochetal growth. Furthermore, a D52A point mutation at the phosphorylation site within the N terminus of Rrp2 abolished cell replication. Mutation of the ATPase motif within the central domain of Rrp2 did not affect spirochetal replication, indicating that phosphorylation-dependent ATPase activity of Rrp2 for σ54activation is not required for cell growth. However, deletion of the C-terminal domain or a 16-amino-acid truncation of the helix-turn-helix (HTH) DNA-binding motif within the C-terminal domain of Rrp2 abolished spirochetal replication. It was shown that constitutive expression ofrpoSis deleterious to borrelial growth. We showed that the essential nature of Rrp2 is not due to an effect onrpoS. These data suggest that phosphorylation-dependent oligomerization and DNA binding of Rrp2 likely function as a repressor, independently of the activation of σ54, controlling an essential step of cell replication inB. burgdorferi.IMPORTANCEBacterial enhancer-binding proteins (bEBPs) are a unique group of transcriptional activators specifically required for σ54-dependent gene transcription. This work demonstrates that theB. burgdorferibEBP, Rrp2, has an additional function that is independent of σ54, that of its essentiality for spirochetal growth, and such a function is dependent on its N-terminal signal domain and C-terminal DNA-binding domain. These findings expand our knowledge on bEBP and provide a foundation to further study the underlying mechanism of this new function of bEBP.

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