scholarly journals A Recurrent Activating Missense Mutation in Waldenström Macroglobulinemia Affects the DNA Binding of the ETS Transcription Factor SPI1 and Enhances Proliferation

2019 ◽  
Vol 9 (6) ◽  
pp. 796-811 ◽  
Author(s):  
Damien Roos-Weil ◽  
Camille Decaudin ◽  
Marine Armand ◽  
Véronique Della-Valle ◽  
M'boyba K. Diop ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Missense Mutation ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Ets Transcription Factor

ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development

1994 ◽  
Vol 14 (5) ◽  
pp. 3292-3309
Author(s):  
M Lopez ◽  
P Oettgen ◽  
Y Akbarali ◽  
U Dendorfer ◽  
T A Libermann
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Gene Family ◽  
B Cell ◽  
Binding Sites ◽  
B Lymphocyte ◽  
Striking Similarity ◽  
Lymphocyte Development ◽  
B Lymphocyte Development ◽  
Ets Transcription Factor

The ets gene family encodes a group of proteins which function as transcription factors under physiological conditions and, if aberrantly expressed, can cause cellular transformation. We have recently identified two regulatory elements in the murine immunoglobulin heavy-chain (IgH) enhancer, pi and microB, which exhibit striking similarity to binding sites for ets-related proteins. To identify ets-related transcriptional regulators expressed in pre-B lymphocytes that may interact with either the pi or the microB site, we have used a PCR approach with degenerate oligonucleotides encoding conserved sequences in all members of the ets family. We have cloned the gene for a new ets-related transcription factor, ERP (ets-related protein), from the murine pre-B cell line BASC 6C2 and from mouse lung tissue. The ERP protein contains a region of high homology with the ETS DNA-binding domain common to all members of the ets transcription factor/oncoprotein family. Three additional smaller regions show homology to the ELK-1 and SAP-1 genes, a subgroup of the ets gene family that interacts with the serum response factor. Full-length ERP expresses only negligible DNA-binding activity by itself. Removal of the carboxy terminus enables ERP to interact with a variety of ets-binding sites including the E74 site, the IgH enhancer pi site, and the lck promoter ets site, suggesting a carboxy-terminal negative regulatory domain. At least three ERP-related transcripts are expressed in a variety of tissues. However, within the B-cell lineage, ERP is highly expressed primarily at early stages of B-lymphocyte development, and expression declines drastically upon B-cell maturation, correlating with the enhancer activity of the IgH pi site. These data suggest that ERP might play a role in B-cell development and in IgH gene regulation.

scholarly journals Cooperative DNA binding by a splice variant of the transcription factor ETS1 that lacks autoinhibition

2016 ◽  
Author(s):  
Daniel Samorodnitsky ◽  
Courtney Szyjka ◽  
Gerald B. Koudelka
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Splice Variant ◽  
Specific Interaction ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Ets Family ◽  
Ets Transcription Factor ◽  
Binding Sequence ◽  
Crucial Part

AbstractETS1 is the archetypal member of the metazoan ETS transcription factor family. All the members of this family bind to the conserved GGA(A/T) core ETS binding sequence (EBS). Several ETS family members exhibit autoinhibition, wherein one domain of ETS blocks its own DNA-binding activity until certain conditions are met. Relief of autoinhibition in these proteins is coupled to homo- or hetero-dimer formation. Relief of autoinhibition in full-length ETS1 is catalyzed by non-specific interaction with DNA, which facilitates the formation of protein dimers.The ETS1 splice variant, ETS1-p42, lacks an exon that encodes a crucial part of the autoinhibitory module. Thus,ETS1-p42 does not autoinhibit. We showed that the absence of autoinhibition allows ETS1Δ335, an N-terminal deletion that recapitulates the DNA-binding of ETS1-p42, to form homodimers in the absence of DNA. However, ETS1-p42 is thought to bind its DNA sites only as monomers. Here, we explore this paradox and show that ETS1Δ335 binds cooperatively to DNA containing two EBSs. We also show that residues in ETS1’s DNA recognition helix mediate this DNA-binding cooperativity. Furthermore we also find that a single EBS can bind two ETS1Δ335 subunits. Finally, we show that DNA acts catalytically to separate unbound ETS1Δ335 dimers into monomers. Together,these results suggest a model of ETS1-p42 DNA-binding, where ETS1-p42 can bind to a single EBS with 2:1 stoichiometry.

Abstract 2954: Mithramycin analogues disrupt ETS transcription factor DNA binding

2019 ◽  
Author(s):  
Reiya C. Hayden ◽  
Caixia Hou ◽  
Prithiba Mitra ◽  
Abhisek Mandal ◽  
Jurgen Rohr ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Ets Transcription Factor

scholarly journals MYD88-independent growth and survival effects of Sp1 transactivation in Waldenström macroglobulinemia

Blood ◽  
2014 ◽  
Vol 123 (17) ◽  
pp. 2673-2681 ◽  
Author(s):  
Mariateresa Fulciniti ◽  
Nicola Amodio ◽  
Rajya Lakshmi Bandi ◽  
Mansa Munshi ◽  
Guang Yang ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcription Factor ◽  
Growth And Survival ◽  
Waldenström Macroglobulinemia ◽  
Sp1 Transcription Factor ◽  
Waldenstrom Macroglobulinemia ◽  
Key Points ◽  
Dual Inhibition

Key Points Sp1 transcription factor (TF) is activated in WM. Dual inhibition of Sp1 and MYD88 pathways induces synergistic cell death in WM cells.

scholarly journals A pathogenic DYT-THAP1 dystonia mutation causes hypomyelination and loss of YY1 binding

2021 ◽  
Author(s):  
Dhananjay Yellajoshyula ◽  
Abigail E Rogers ◽  
Audrey J Kim ◽  
Sumin Kim ◽  
Samuel S Pappas ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Missense Mutation ◽  
Transcriptional Activity ◽  
Molecular Pathogenesis ◽  
Active Transcription ◽  
Cns Myelination ◽  
Established Role

Dystonia is a disabling disease that manifests as prolonged involuntary twisting movements. DYT-THAP1 is an inherited form of isolated dystonia caused by mutations in THAP1 encoding the transcription factor THAP1. The phe81leu (F81L) missense mutation is representative of a category of poorly understood mutations that do not occur on residues critical for DNA binding. Here, we demonstrate that the F81L mutation (THAP1F81L) impairs THAP1 transcriptional activity and disrupts CNS myelination. Strikingly, THAP1F81L exhibits normal DNA binding but causes a significantly reduced DNA binding of YY1, its transcriptional partner that also has an established role in oligodendrocyte lineage progression. Our results suggest a model of molecular pathogenesis whereby THAP1F81L normally binds DNA but is unable to efficiently organize an active transcription complex.

scholarly journals Mithramycin analogues disrupt ETS transcription factor DNA binding

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Reiya Cherron Hayden ◽  
Caixia Hou ◽  
Abhisek Mandal ◽  
Prithiba Mitra ◽  
Jon Thorson ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Ets Transcription Factor

Abstract 2954: Mithramycin analogues disrupt ETS transcription factor DNA binding

2019 ◽  
Author(s):  
Reiya C. Hayden ◽  
Caixia Hou ◽  
Prithiba Mitra ◽  
Abhisek Mandal ◽  
Jurgen Rohr ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Ets Transcription Factor

scholarly journals ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development.

1994 ◽  
Vol 14 (5) ◽  
pp. 3292-3309 ◽  
Author(s):  
M Lopez ◽  
P Oettgen ◽  
Y Akbarali ◽  
U Dendorfer ◽  
T A Libermann
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Gene Family ◽  
B Cell ◽  
Binding Sites ◽  
B Lymphocyte ◽  
Striking Similarity ◽  
Lymphocyte Development ◽  
B Lymphocyte Development ◽  
Ets Transcription Factor

The ets gene family encodes a group of proteins which function as transcription factors under physiological conditions and, if aberrantly expressed, can cause cellular transformation. We have recently identified two regulatory elements in the murine immunoglobulin heavy-chain (IgH) enhancer, pi and microB, which exhibit striking similarity to binding sites for ets-related proteins. To identify ets-related transcriptional regulators expressed in pre-B lymphocytes that may interact with either the pi or the microB site, we have used a PCR approach with degenerate oligonucleotides encoding conserved sequences in all members of the ets family. We have cloned the gene for a new ets-related transcription factor, ERP (ets-related protein), from the murine pre-B cell line BASC 6C2 and from mouse lung tissue. The ERP protein contains a region of high homology with the ETS DNA-binding domain common to all members of the ets transcription factor/oncoprotein family. Three additional smaller regions show homology to the ELK-1 and SAP-1 genes, a subgroup of the ets gene family that interacts with the serum response factor. Full-length ERP expresses only negligible DNA-binding activity by itself. Removal of the carboxy terminus enables ERP to interact with a variety of ets-binding sites including the E74 site, the IgH enhancer pi site, and the lck promoter ets site, suggesting a carboxy-terminal negative regulatory domain. At least three ERP-related transcripts are expressed in a variety of tissues. However, within the B-cell lineage, ERP is highly expressed primarily at early stages of B-lymphocyte development, and expression declines drastically upon B-cell maturation, correlating with the enhancer activity of the IgH pi site. These data suggest that ERP might play a role in B-cell development and in IgH gene regulation.

Sign in / Sign up

Export Citation Format

Share Document