Heterodimers, targeting

Die l4-3-3s are a family of 30 kDa proteins that exist as homo- and heterodimers within all eukaryotic cells. 14-3-3 proteins bind target proteins containing phospho-threonine or phosphoserine motifs, however exceptions do exist. Die docking of 14-3-3s to their target can ... 

Fig. 3.14 Model for polyamide inhibition of the p55/p50 heterodimeric transcription factor NF-kB. Polyamides designed to target both the p65 and p50 DNA subsites (NF-kB site in bracket) demonstrated that only those targeting the p50 subsite effectively inhibit heterodimer binding. Symbols are defined in Fig. 3.4...

K, Alder, F, Smith, A, McKernan, R, Metters, K, O Neill, GP, Facaille, JC and Hebert TE (2001) y-Aminobutyric acid type B receptors with specific heterodimer composition and postsynaptic actions in hippocampal neurons are targets of anticonvulsant gabapentin action. Mol. Pharmacol. 59 144-152. 

This same strategy can be attempted at the mRNA level to inhibit the translation of individual mRNAs. These experiments are almost never 100% efficient hence, the problem becomes how much neutralization is necessary to elicit the desired effect. If the antisense oligonucleotide is targeted toward the mRNA for a particular transcription factor or splice form of a transcription factor, then it may be possible to knock down or reduce the expression of that particular protein. The result of such a knockdown will be a new balance of transcription factor subunits in the cell, probably resulting in alteration of the relative amounts of particular homo- and heterodimers. 

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