Discovery of a small-molecule inhibitor of the KIX-KID interaction.
Bingbing X. Li,Xiangshu Xiao +1 more
TLDR
Protein–protein interactions are essential for transmitting signals from extracellular space to cell nuclei and also for cell–cell communication and potential therapeutics for many different human diseases.Abstract:
Protein–protein interactions are essential for transmitting signals from extracellular space to cell nuclei and also for cell–cell communication. Small molecules that target protein–protein interactions, therefore, are great research tools for dissecting the biological functions of a given protein–protein interaction and potential therapeutics for many different human diseases.[1] However, targeting protein–protein interactions by small molecules remains a significant challenge.[1, 2]read more
Citations
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Protein lysine acetylation by p300/CBP.
Beverley M. Dancy,Philip A. Cole +1 more
TL;DR: The current understanding of p300/CBP is summarized including the novel technologies developed for these studies, which revealed that acetyl-CoA binds in a tunnel enclosed by a unique loop, while the substrate protein transiently associates with an acidic patch, following a hit-and-run kinetic mechanism.
Journal ArticleDOI
Transcriptional/epigenetic regulator CBP/p300 in tumorigenesis: structural and functional versatility in target recognition.
Feng Wang,Feng Wang,Feng Wang,Christopher B. Marshall,Christopher B. Marshall,Mitsuhiko Ikura,Mitsuhiko Ikura +6 more
TL;DR: Recent exciting findings in the structural mechanisms of CBP/p300 involving multivalent and dynamic interactions with binding partners, which may pave new avenues for anti-cancer drug development are focused on.
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Targeting CREB for cancer therapy: friend or foe.
TL;DR: The results suggest that CREB is a suitable transcription factor for drug targeting and therefore targeting CREB could represent a novel strategy for cancer therapy.
Journal ArticleDOI
CREB Family Transcription Factors Are Major Mediators of BDNF Transcriptional Autoregulation in Cortical Neurons
TL;DR: It is shown that extensive BDNF transcriptional autoregulation, encompassing all major BDNF transcripts, occurs also in vivo in the adult rat hippocampus during BDNF-induced LTP, and the existence of a stimulus-specific distal enhancer modulating BDNF gene expression is suggested.
Journal ArticleDOI
Identification of a Potent Inhibitor of CREB-Mediated Gene Transcription with Efficacious in Vivo Anticancer Activity
Fuchun Xie,Bingbing X. Li,Alina Kassenbrock,Changhui Xue,Xiaoyan Wang,David Z. Qian,Rosalie C. Sears,Xiangshu Xiao +7 more
TL;DR: Biological evaluations of a series of structural congeners of naphthamide 3a uncovered compound 3i (666-15) as a potent and selective inhibitor of CREB-mediated gene transcription and potently inhibited cancer cell growth without harming normal cells.
References
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Journal ArticleDOI
CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals.
TL;DR: The molecular mechanisms by which Ser133-phosphorylated CREB activates transcription, intracellular signaling pathways that lead to phosphorylation ofCREB at Ser133, and features of each signaling pathway that impart specificity at the level of CREB activation are discussed.
Journal ArticleDOI
Reaching for high-hanging fruit in drug discovery at protein–protein interfaces
TL;DR: These studies discovered small molecules that bind with drug-like potencies to 'hotspots' on the contact surfaces involved in protein–protein interactions, and bind with much higher efficiencies than do the contact atoms of the natural protein partner.
Journal ArticleDOI
Ca2+ Influx Regulates BDNF Transcription by a CREB Family Transcription Factor-Dependent Mechanism
TL;DR: The findings suggest that a CREB family member acts cooperatively with an additional transcription factor(s) to regulate BDNF transcription, and concludes that the BDNF gene is aCREB family target whose protein product functions at synapses to control adaptive neuronal responses.
Journal ArticleDOI
Scissors-grip model for DNA recognition by a family of leucine zipper proteins
TL;DR: An evaluation of the properties of conserved amino acids within the basic region of 11 deduced protein sequences, coupled with the observation that they are located at an invariant distance from the leucine zipper, has led to the formulation of a "scissors-grip" model for DNA binding.
Journal ArticleDOI
Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions.
Ishwar Radhakrishnan,Gabriela C. Pérez-Alvarado,David Parker,H. Jane Dyson,Marc Montminy,Peter E. Wright +5 more
TL;DR: The solution structure of the complex formed by the phosphorylated kinase-inducible domain (pKID) of CREB with KIX reveals that pKID undergoes a coil-->helix folding transition upon binding to KIX, forming two alpha helices.
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