Sequence Specific DNA Binding of Ets-1 Transcription Factor: Molecular Dynamics Study on the Ets Domain–DNA Complexes

Obika, Satoshi; Reddy, Swarnalatha Y.; Bruice, Thomas C.

doi:10.1016/s0022-2836(03)00726-5

Cited by 23 publications

(24 citation statements)

References 52 publications

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“…Ets factors bind to the GGAA/T core motif (Ets-binding site, EBS) in the enhancer or promoter regions of their target genes (Sementchenko and Watson, 2000;Dittmer, 2003;Obika et al, 2003). ETS1 is involved in cell differentiation, proliferation, lymphoid cell development, transformation, apoptosis, angiogenesis, motility and invasion (Li et al, 1999;Kavurma et al, 2002;Watson et al, 2002;Xu et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion

Yordy

Sementchenko

et al. 2004

Oncogene

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The ETS1 transcription factor is a member of the Ets family of conserved sequence-specific DNA-binding proteins. ETS1 has been shown to play important roles in various cellular processes such as proliferation, differentiation, lymphoid development, motility, invasion and angiogenesis. These diverse roles of ETS1 are likely to be dependent on specific protein interactions. To identify proteins that interact with ETS1, a yeast two-hybrid screen was conducted. Here, we describe the functional interaction between SP100 and ETS1. SP100 protein interacts with ETS1 both in vitro and in vivo. SP100 is localized to nuclear bodies and ETS1 expression alters the nuclear body morphology in living cells. SP100 negatively modulates ETS1 transcriptional activation of the MMP1 and uPA promoters in a dose-dependent manner, decreases the expression of these endogenous genes, and reduces ETS1 DNA binding. Expression of SP100 inhibits the invasion of breast cancer cells and is induced by Interferon-a, which has been shown to inhibit the invasion of cancer cells. These data demonstrate that SP100 modulates ETS1-dependent biological processes.

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Section: Introductionmentioning

confidence: 99%

SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion

Yordy

Sementchenko

et al. 2004

Oncogene

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“…It is unclear which of these activities is most crucial for Ets1 to inhibit ASC differentiation or if they both play partial roles. To explore whether or not direct binding of Ets1 to DNA is important for its activity in blocking ASC formation, we generated mutant versions of Ets1 in which we altered highly conserved arginine residues (R391 and R394) within the Ets domain that are found in helix H3 and known to interact with nucleotide bases within the core Ets target sequence GGA A / T (27)(28)(29). As expected, these mutations completely abolished Ets1 DNA binding in EMSAs (Fig.…”

Section: Ets1 But Not Ets2 Inhibits Asc Differentiationmentioning

confidence: 67%

Transcription Factor Ets1, but Not the Closely Related Factor Ets2, Inhibits Antibody-Secreting Cell Differentiation

John

Russell

Chin

et al. 2014

Molecular and Cellular Biology

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bB cell differentiation into antibody-secreting cells (ASCs) is a tightly regulated process under the control of multiple transcription factors. One such transcription factor, Ets1, blocks the transition of B cells to ASCs via two separate activities: (i) stimulating the expression of target genes that promote B cell identity and (ii) interfering with the functional activity of the transcription factor Blimp1. Ets1 is a member of a multigene family, several members of which are expressed within the B cell lineage, including the closely related protein Ets2. In this report, we demonstrate that Ets1, but not Ets2, can block ASC formation despite the fact that Ets1 and Ets2 bind to apparently identical DNA sequence motifs and are thought to regulate overlapping sets of target genes. The DNA binding domain of Ets1 is required, but not sufficient by itself, to block ASC formation. In addition, less conserved regions within the N terminus of Ets1 play an important role in inhibiting B cell differentiation. Differences between the N termini of Ets1 and Ets2, rather than differences in the DNA binding domains, determine whether the proteins are capable of blocking ASC formation or not.

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“…For further information on the current status in modeling of protein structures and interactions, the reader is referred to a recent review (Schueler-Furman et al,2005). Based on structure models, molecular dynamics simulation have shown to be a versatile tool to investigate the dynamic behavior of complexes between DNA binding sites and respective DNA target sites (Marco et al, 2003;;Obika et al,2003). These tools can also be employed to predict the effect of structural modulations on protein-ligand interactions in a way that would allow forward-engineering design of, e.g.…”

Section: Design Of Functions and Interactions Of Macromoleculesmentioning

confidence: 99%

Promising Role of Engineered Gene Circuits in Gene Therapy

Wang¹,

Lang²

2011

Gene Therapy - Developments and Future Perspectives

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Sequence Specific DNA Binding of Ets-1 Transcription Factor: Molecular Dynamics Study on the Ets Domain–DNA Complexes

Cited by 23 publications

References 52 publications

SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion

SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion

Transcription Factor Ets1, but Not the Closely Related Factor Ets2, Inhibits Antibody-Secreting Cell Differentiation

Promising Role of Engineered Gene Circuits in Gene Therapy

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