Article

When Ets transcription factors meet their partners.

CNRS UMR 8526, Institut de Biologie de Lille, B.P. 447, 1 rue Calmette, 59021 Lille Cedex, France.
BioEssays (Impact Factor: 5.42). 05/2002; 24(4):362-70. DOI: 10.1002/bies.10068
Source: PubMed

ABSTRACT Ets proteins are a family of transcription factors that regulate the expression of a myriad of genes in a variety of tissues and cell types. This functional versatility emerges from their interactions with other structurally unrelated transcription factors. Indeed, combinatorial control is a characteristic property of Ets family members, involving interactions between Ets and other key transcriptional factors such as AP1, SRF, and Pax family members. Intriguingly, recent molecular modeling and crystallographic data suggest that not only the ETS DNA-binding domain, but also the DNA recognition helix alpha3, are often directly required for Ets partner's selection. Indeed, while most DNA-binding proteins appear to exploit differences within their DNA recognition helices for sites selection, the Ets proteins exploit differences in their surfaces that interact with other transcription factors, which in turn may modify their DNA-binding properties in a promoter-specific fashion. Taken together, the gene-specific architecture of these unique complexes can mediate the selective control of transcriptional activity.

0 Bookmarks
 · 
64 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interstitial collagenase-1 degrades a variety of extracellular matrix components. A single guanine insertion polymorphism in the promoter has been found that influences on the transcription and expression level of the gene. It is suggested that this polymorphism may enhance susceptibility to some types of cancer. Therefore, this case-control study evaluated the association of this genotype polymorphism with susceptibility to initiation and invasion of colorectal cancer. For this reason, whole blood samples were obtained from 150 CRC patients and 100 control subjects in Tehran. Genomic DNA was extracted and genotyped by PCR-RFLP method. We showed that 2G allele and 2G/2G genotype had higher frequencies in patients (60% and 39%, respectively) than in controls (47% and 23%, respectively). The CRC patients were divided into two groups: with metastasis (M+) and without metastasis (M-) groups. The 2G allele was more frequent in M+ group compared with control group. However, no significantly difference was observed between M-group and control (chi(2) = 0.48, P = 0.78 for 2G/2G genotype). Further stratification analyses showed that only gender (OR = 2.58, 95% CI = 0.89-7.52 for women and OR = 4.12, 95% CI = 1.62-10.42 for men) and smoking (OR = 3.03, 95% CI = 1.28-7.16 for non-smokers and OR = 4.09, 95% CI = 1.18-4.15 for smoker) may modify the risk of colorectal invasion related to 2G/2G genotype. Furthermore, individual with 2G/2G genotype seems to spread metastasis, 3 years earlier than those who were 1G/1G and 1G/2G. In conclusion, to our knowledge, the present epidemiological study for the first time indicates the relationship of 2G/2G genotype polymorphism with invasion risk of colorectal cancer in subgroups of gender and smoking, especially in smoker men.
    Cancer Investigation 10/2008; 26(8):836-42. · 2.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Induction of type I interferon is a central event of innate immunity, essential for host defense. Here we report that the transcription factor ELF4 is induced by type I interferon and upregulates interferon expression in a feed-forward loop. ELF4 deficiency leads to reduced interferon production, resulting in enhanced susceptibility to West Nile virus encephalitis in mice. After viral infection, ELF4 is recruited by STING, interacts with and is activated by the MAVS-TBK1 complex, and translocates into the nucleus to bind interferon promoters. Cooperative binding with ELF4 increases the binding affinity of interferon regulatory factors IRF3 and IRF7, which is mediated by EICE elements. Thus, in addition to identifying a regulator of innate immune signaling, we uncovered a role for EICE elements in interferon transactivation.
    Nature Immunology 11/2013; · 26.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Ets family of eukaryotic transcription factors is based around the conserved Ets DNA-binding domain. Although their DNA-binding selectivity is biochemically and structurally well characterized, structures of homodimeric and ternary complexes point to Ets domains functioning as versatile protein-interaction modules. In the present paper, we review the progress made over the last decade to elucidate the structural mechanisms involved in modulation of DNA binding and protein partner selection during dimerization. We see that Ets domains, although conserved around a core architecture, have evolved to utilize a variety of interaction surfaces and binding mechanisms, reflecting Ets domains as dynamic interfaces for both DNA and protein interaction. Furthermore, we discuss recent advances in drug development for inhibition of Ets factors, and the roles structural biology can play in their future.
    Biochemical Society Transactions 02/2014; 42(1):130-8. · 2.59 Impact Factor