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. 2015 Dec;11(12):891-4.
doi: 10.1038/nchembio.1962.

Targeting transcription is no longer a quixotic quest

Anna K Mapp  1 , Rachel Pricer  1 , Steven Sturlis  1
Affiliations

Targeting transcription is no longer a quixotic quest

Anna K Mapp et al. Nat Chem Biol. 2015 Dec.

Abstract

Misregulated transcription factors play prominent roles in human disease, but their dynamic protein-protein interaction network has long made the goal of transcription-targeted therapeutics impractical. Recent advances in technologies for modulating protein interaction networks mean that the end of the quest is in sight.

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Figures

Figure 1
Figure 1
The chemical space of protein-protein interactions. (a) Protein-protein interactions can be effectively classified by the strength of the complex (y-axis) and the surface area over which the interaction occurs (x-axis). Using p53 as an example, transcriptional activator interaction networks span a broad range of strength and surface area. PBD ID codes for each structure are as follows: p53-Mdm2 repressor, PDB 1YCR; p53 dimer, PDB 1PET; GACKIX domain of CBP with proposed binding residues, PDB 2LQH. (b) Recent advances in protein-protein interaction inhibitor design and screening methodologies have led to the discovery of a number of new small-molecule inhibitors, although success in targeting high-affinity, small-surface-area interactions has far outpaced broader or weaker interactions. SA, surface area. See refs. and for a more detailed discussion.
Figure 2
Figure 2
Transcription complexes are dynamic in composition and conformation. (a) The BAF chromatin remodeling complexes contain the same enzymatic core (BRG1) but have exchangeable subunits such as BAF45a and BAF45b that define tissue specificity. See ref. for a more complete discussion of the composition and function of these complexes. (b) The GACKIX (Gal11, Arc105, CBP/p300, kinase-inducible domain interacting) motif of CBP/p300 uses two binding sites to interact with more than 10 distinct transcriptional activators. (c) Each ternary complex has a signature conformation with the two binding sites in allosteric communication. The structure and function of the GACKIX motif were recently reviewed in ref. .
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References

    1. Jacob F, Monod J. J. Mol. Biol. 1961;3:318–356. - PubMed
    1. Lin CY, et al. Cell. 2012;151:56–67. - PMC - PubMed
    1. Pattabiraman DR, et al. Blood. 2014;123:2682–2690. - PubMed
    1. Khoo KH, Verma CS, Lane DP. Nat. Rev. Drug Discov. 2014;13:217–236. - PubMed
    1. Kar A, Gutierrez-Hartmann A. Crit. Rev. Biochem. Mol. Biol. 2013;48:522–543. - PMC - PubMed

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