Eukaryotes transcription factors

Nuclear factor kappa B (NF-kB) is the generic term for a family of dimeric eukaryotic transcription factors, composed of members of the Rel family of DNA-binding proteins including the mammalian proteins RelA (or p65), cRel, RelB, p50 and p52, and the Drosophila proteins Dorsal, Dif and Relish. These proteins bind with different affinities to a consensus DNA sequence motif (called the kB site) consisting of the sequence 5 -GGGRNNYYCC-3 in which R is a purine, Y is a pyrimidine, and N is any base. 

The Rel homology domain (RHD) is an evolutionarily conserved domain found in some eukaryotic transcription factors, including NF-kB, the nuclear factors of activated T-cells (NFATs) and the drosophila proteins Dif and Relish. Some of these transcription factors form... 

Tab. 13.1 Transcription factors under the control of RNI. Selected examples for the regulatory impact of RNI on prokaryotic and eukaryotic transcription factors. In a very simplistic way activation versus inhibition by RNI are indicated.

Rodriguez, J. M., Salas, M. L., and Vinuela, E. Genes homologous to ubiquitin-conjugating proteins and eukaryotic transcription factor SII in African swine fever virus. Virology 1992, 386, 40-52. 

Sandelin, A., Alkema, W., Engstrom, P.,Wasserman, W. W., andLenhard, B. (2004) JASPAR an open-access database for eukaryotic transcription factor binding profiles. Nucleic Acids Res. 32, D91-D94. 

The eukaryotic transcription factor NFxB also binds DNA via P-sheet structure (Fig. 1.10). Noteworthy is the enshrouding of the DNA by the P-sheets of NFxB. The recognition of the DNA elements is also achieved by interaction with the major groove of the DNA. 

Burley, S.K. DNA-binding motifs from eukaryotic transcription factors (1994) Curr. Op. Struct. Biol. 4, 3-11... 

Subunit Mixing in Eukaryotic Regulatory Proteins Several families of eukaryotic transcription factors have been defined based on close structural similarities. Within each family, dimers can sometimes form between two identical proteins (a homodimer) or between two different members of the family (a heterodimer). A hypothetical family of four different leucine-zipper proteins could thus form up to ten different dimeric species. In many cases, the different combinations appear to have distinct regulatory and functional properties. 

Discuss two main DNA-recognition motifs found in eukaryotic transcription factors. Describe their structures, indicate how they bind to DNA, and discuss how each specifically recognizes its DNA binding site. 

Discuss the types of structural motifs found in eukaryotic transcription factors. 

Figure 15.3 Resveratrol modulation of pro-inflammatory signaling pathways. Resver-atrol represses transcriptional activation of various pro-inflammatory genes by inhibiting pro-inflammatory stimuli-induced activation of upstream kinases, such as MAP kinases, PI3K/Akt, IKK, PKC, etc., and blocking the DNA binding of eukaryotic transcription factors, such as NF-kB, AP-1, and STAT3.

An important eukaryotic transcription factor is the nuclear factor, NF-kB (NF-xB). This factor binds to DNA through i-sheets. The i-sheets of the dimeric transcription factor wrap around the DNA like a mantle. Contacts are made, as in the case of a-helices, with die major groove of the DNA. The structure is shown in Plate 18. 

M. Chytil and G. L. Verdine. The Rel family of eukaryotic transcription factors. Curr Opin Struct Biol, 6, 91-100, 1996. 

D. S. I dman. Eukaryotic transcription factors. Chapter 7 Transcripuon factors and cancer, pp. 153-176. Academic Press, London, 1991. 

L. Chen. 1999. Combinatorial gene regulation by eukaryotic transcription factors Curr. Opin. Struct. Biol. 9 48-55. (PubMed)... 

We have seen how interactions between DNA-binding proteins such as CAP and RNA polymerase can activate transcription in prokaryotic cells (Section 31.1.6). Such protein-protein interactions play a dominant role in eukaryotic gene regulation. In contrast with those of prokaryotic transcription, few eukaryotic transcription factors have any effect on transcription on their own. Instead, each factor recruits other proteins to build up large complexes that interact with the transcriptional machinery to activate or repress Panscription. 

Latchman, D. S., 1999. Eukaryotic Transcription Factors (3rd ed.). Academic Press. 

R. Schreck, and P. A. Baeuerle, Assessing oxygen radicals as mediators in activation of inducible eukaryotic transcription factor NF-kappa B, Methods Enzymot. 234 (1994) 151-163. 

Methylcytosine The 5-methyl hydrophobic effect was used to inhibit the recognition of double-hehcal DNA by prokaryotic modifying enzymes and a eukaryotic transcription factor via ohgonucleotide-directed triple-helix formation in which ODNs containing m C conferred substantially more efficient inhibition than those with C [22]. Triple-heUx formation also selectively protects the DNA duplex from restriction methylation, and the specificity of 15 base pairs is useful for chromosome mapping. 

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