Pharmacological manipulation of transcription factor protein-protein interactions: opportunities and obstacles

Fontaine, Frank, Overman, Jeroen and Francois, Mathias (2015) Pharmacological manipulation of transcription factor protein-protein interactions: opportunities and obstacles. Cell Regeneration, 4 2: 2. doi:10.1186/s13619-015-0015-x

Author Fontaine, Frank
Overman, Jeroen
Francois, Mathias
Title Pharmacological manipulation of transcription factor protein-protein interactions: opportunities and obstacles
Journal name Cell Regeneration   Check publisher's open access policy
ISSN 2045-9769
Publication date 2015-12-01
Sub-type Article (original research)
DOI 10.1186/s13619-015-0015-x
Open Access Status DOI
Volume 4
Issue 2
Start page 2
Total pages 12
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Subject 1307 Cell Biology
1309 Developmental Biology
Abstract Much research on transcription factor biology and their genetic pathways has been undertaken over the last 30 years, especially in the field of developmental biology and cancer. Yet, very little is known about the molecular modalities of highly dynamic interactions between transcription factors, genomic DNA, and protein partners. Methodological breakthroughs such as RNA-seq (RNA-sequencing), ChIP-seq (chromatin immunoprecipitation sequencing), RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins), and single-molecule imaging will dramatically accelerate the discovery rate of their molecular mode of action in the next few years. From a pharmacological viewpoint, conventional methods used to target transcription factor activity with molecules mimicking endogenous ligands fail to achieve high specificity and are limited by a lack of identification of new molecular targets. Protein-protein interactions are likely to represent one of the next major classes of therapeutic targets. Transcription factors, known to act mostly via protein-protein interaction, may well be at the forefront of this type of drug development. One hurdle in this field remains the difficulty to collate structural data into meaningful information for rational drug design. Another hurdle is the lack of chemical libraries meeting the structural requirements of protein-protein interaction disruption. As more attempts at modulating transcription factor activity are undertaken, valuable knowledge will be accumulated on the modality of action required to modulate transcription and how these findings can be applied to developing transcription factor drugs. Key discoveries will spawn into new therapeutic approaches not only as anticancer targets but also for other indications, such as those with an inflammatory component including neurodegenerative disorders, diabetes, and chronic liver and kidney diseases.
Keyword Transcription
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: Scopus Citation Count Cited 12 times in Scopus Article | Citations
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Created: Wed, 16 Dec 2015, 20:53:56 EST by Susan Allen on behalf of Institute for Molecular Bioscience