Transcription factors activating domains

No common structural motifs are known for the activation domains of transcription factors. Activation domains that are rich in acidic amino acids, glutamines or prolines have been reported. 

Figure 1 The classic yeast two-hybrid method and derivatives, (a) Schematic diagram of the yeast two-hybrid approach, describing an interaction between protein X and protein Y. Protein X is fused to a transcription factor DNA-binding domain (the "bait" construct), and protein Y is fused to a transcription factor activation domain (the "prey" construct), (b) High-throughput applications of the yeast two-hybrid method use mating of haploid strains carrying bait and prey, respectively. Hybrids can be mated in arrayed formats (as shown) or as libraries, (c) The reverse two-hybrid method uses a counter-selectable marker to indicate loss of protein interaction because of disruption by an inhibitor protein/small molecule ("/" illustrated in the diagram) or mutation(s) in proteins X and/or Y.

Fig. 8. Models showing the involvement of AP2/ERF-domain transcription factors in regulation of stress and defense gene expression in plants. The stress signal is perceived by interaction with a receptor (-kinase). Induction of de novo synthesis and/or modulation of the preexisting AP2/ERF-domain transcription factor activate gene expression. Unidentified signal transduction components are indicated with a question mark. Dashed arrows indicate the possible involvement of multiple signalling steps...

The biological consequences of the interaction of pTyr-containing proteins with SH2-domain proteins depend on the function of the protein recruited. Thus, a phosphorylation-dephosphorylation cascade may be activated by recruitment of a kinase or a phosphatase, or a target enzyme maybe stimulated which produces a second messenger in response to a receptor signal,25 or signalling proteins may be relocated and transcription factors activated.26 Eventually, most of these events lead to the activation of gene transcription. 

The polypeptide chain of p53 is divided in three domains, each with its own function (Figure 9.16). Like many other transcription factors, p53 has an N-terminal activation domain followed by a DNA-binding domain, while the C-terminal 100 residues form an oligomerization domain involved in the formation of the p53 tetramers. Mutants lacking the C-terminal domain do not form tetramers, but the monomeric mutant molecules retain their sequence-specific DNA-binding properties in vitro. 

Activator Protein-1 (API) comprises transcriptional complexes formed by dimers of members oftheFos, Jun, and ATF family of transcription factors. These proteins contain basic leucine zipper domains that mediate DNA binding and dimerization. They regulate many aspects of cell physiology in response to environmental changes. 

Sequence-specific transcription factors often bind as multimers especially as dimers to DNA. This allows binding of mirror-imaged sequences (palindromes) in the DNA that are separated by a few spacer nucleotides. The dimerization is stabilized by hydrophobic motifs within dimerization motifs of each transcription factor molecule. Dependent on the nature of the dimerization domain and the abundance of individual transcription factors homo- or heterodimers can form and bind to palindromes with differential activity. 

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