Understanding p300-transcription factor interactions using sequence variation and hybridization

Abstract

The hypoxic response is central to cell function and plays a significant role in the growth and survival of solid tumours. HIF-1 regulates the hypoxic response by activating over 100...

Cited2 is a key regulator of placental development and plasticity

“…[76] CITED2 also has a higher affinity than HIF1A for EP300, and unidirectionally displaces HIF1A from its association with EP300. [102] CITED2 has also been shown to interact with other proteins, including LIM homeobox 2, [2] TFAP2 family transcription factors, [5] SMAD family members 2 and 3, [103] peroxisome proliferator-activated receptor gamma (PPARG), [7] estrogen receptor, [104] MYC proto-oncogene, bHLH transcription factor, [105] and nucleolin. [106] Several parameters of CITED family protein interactions with the TFAP2 family have been discerned.…”

“…[ 76 ] CITED2 also has a higher affinity than HIF1A for EP300, and unidirectionally displaces HIF1A from its association with EP300. [ 102 ]…”

Site-directed allostery perturbation to probe the negative regulation of hypoxia inducible factor-1α

“…The cooperative folding/binding of the CITED2 binding motifs drives the displacement of HIF-1a and results in an allosteric conformational change that favours the CITED2-bound state, rendering the competition virtually irreversible. [22][23][24][25][26][27][28][29] a University of Szeged, Department of Medical Chemistry, 8 Do ´m te ´r, Szeged, 6720, Hungary. E-mail: martinek.tamas@med.u-szeged.hu, hegedus.zsofia@med.uszeged.hu b HUN-REN SZTE Biomimetic Systems Research Group, 8 Do ´m te ´r, Szeged, 6720, Hungary † Electronic supplementary information (ESI) available.…”

“…20,21 Even though CITED2 and HIF-1a have similar binding affinities to p300/CBP, the competition is so efficient that CITED2 completely displaces HIF-1a in a switch-like, irreversible mechanism, allowing the precise regulation of the hypoxic response. 22 Several experimental [22][23][24][25] and molecular modelling studies [26][27][28][29] investigated the underlying structural mechanism of this competition. These works agreed on basic concepts but highlighted different key determinants or provided alternative explanations for the virtually irreversible competition.…”

“…The cooperative folding/binding of the CITED2 binding motifs drives the displacement of HIF-1a and results in an allosteric conformational change that favours the CITED2-bound state, rendering the competition virtually irreversible. [22][23][24][25][26][27][28][29] Several factors play an important role in this complex inhibitory mechanism. These include differences in binding thermodynamics, 25 displacement kinetics, 22,32 and intramolecular cooperativity between binding motifs.…”