Cooperativity factor alpha. For example, the enzyme may Figure 6.

Cooperativity factor alpha. Mol Endocrinol. The cooperativity factor α>1 denotes a positive cooperativity; α<1 results in negative cooperativity; neutral cooperativity occurs in cases where α = 1. Cooperativity occurs at distances that imply the absence of protein-protein interactions between the factors. The chelate effect is the most common origin of positive cooperativity, yet its significance has been widely overlooked. It should be noted that ATCM details the action of all allosteric modulators (not just enhancers) on the binding of orthosteric ligands to GPCRs but not on the signaling. When α is greater than 1, there is a positive cooperativity, whereas a value less than 1 indicates negative cooperativity between the first and second binding events on the same path within the equilibrium diagram. be a protein dimer, composed of two identical sub-proteins with identical binding sites for S. Here, Jin et al. Jan 6, 2023 · Proteolysis targeting chimera (PROTAC) is a novel drug modality that facilitates the degradation of a target protein by inducing proximity with an E3 ligase. 2019; 9: 6501 – 16. The letter, S, denotes the stimulus imparted by a ligand-occupied receptor to the cell. Figure 4. ˜ 5 (a) the spikes to 0 near an instability as well as the decreases in degree of cooperativity occur at the same energies ω 𝐤 \omega_ {\mathbf {k}}. In addition to the commonly used Hill coefficient, other characteristics such as a sigmoidal shape of the overall titration curve in a linear plot, a change of ligand affinity of the other binding sites when Jan 21, 2020 · Li, J. 2. . S4, S5). Keywords: Cooperative binding, Cooperativity, Sep 23, 2009 · Chelate cooperativity in self-assembled structures results in denaturation behavior that is indistinguishable from allosteric ligand binding. Abstract Cooperativity is a widely used chemical concept whose existence is ubiquitous in chemical and biological systems but whose quantification is still controversial and origin much less appreciated. MEROPS, the peptidase database, does not yet list any peptidic or proteinaceous CPAF substrates. Open in a new tab Goto, N. As ligands bind to the protein, the protein's affinity for the ligand decreases. Jun 1, 2019 · The affinity of the inhibitor for the ES complex may differ from its affinity for E by the thermodynamic cooperativity factor α. The role of hepatocyte nuclear factor-3 alpha (Forkhead Box A1) and androgen receptor in transcriptional regulation of prostatic genes. Unlike the concerted model, the sequential model accounts for different species of the protein molecule. show that because FOXA1 promotes AR Abstract Cooperative binding pervades Nature. The thermodynamically complete description of allosteric modulation of receptor activation is described by the CTC model (Fig. Our data present the first structural evidence for the allosteric regulation in smaller GDHs. The symbol, β, describes an activation cooperativity factor, which quantifies the allosteric effect of the modulator on the signalling efficacy of the orthosteric agonist. Honokiol: an effective inhibitor of tumor necrosis factor-alpha-induced up-regulation of inflammatory cytokine and chemokine production in human synovial fibroblasts. Allosteric Modulation (Cooperativity) Cooperativity is a phenomenon displayed by enzymes or receptors that have multiple binding sites where the affinity of the binding sites for a ligand is increased, positive cooperativity, or decreased, negative cooperativity, upon the binding of a ligand to a binding site. 1 day ago · The conditions for cooperativity and criticality for p p -polarized modes are the same as for s s -polarized modes and thus in Fig. Feb 5, 2024 · Furthermore, the cooperativity of binding can be directly calculated through these assays, which gives the cooperativity factor Alpha as a quantitative and comparable indicator to evaluate the ternary complex formation. One can thus foresee that the optical activity The muscarinic M(2) receptor contains an orthosteric and an allosteric site. This cooperativity promotes the integration of cellular and positional identity programs and contributes to the evolution The increased throughput for the agonist shift assay is the first demonstration of allostery measurements on this scale, which were analyzed in an automated manner to produce quantifiable measurements of allostery: alpha (cooperativity factor), beta (efficacy), tauB (direct agonist activity of the allosteric ligand), and KB (intrinsic binding Oct 10, 2021 · Cooperativity is an important parameter to understand the ternary complexes formed by protein degraders. In general, molecular binding is an interaction between molecules that results in a stable physical association between those molecules. Jun 27, 2013 · Cooperativity can be positive (supralinear) or negative (infralinear). The relationship between glyceraldehyde-3-phosphate and the enzyme glyceraldehyde-3-phosphate dehydrogenase is a clear example of this process. , Zor, T. We will model cooperativity by assuming that an enzyme has two separated but indistinguishable binding sites for a substrate S. Schematic model represents the cooperativity in AnGDH. Cooperativity Factor The difference in the ligands of each tertiary atom is due mainly to the different length of chain segments to which it is bonded. K. The stabilization of PPIs is a versatile and emerging therapeutic strategy to target specific combinations of protein partners within the protein interactome. A cartoon of this enzyme is shown in Fig This assay is used to determine the ternary complex affinity ( KD,ternary value) and cooperativity factor alpha ( ) of test compounds between His6-CRBN-DDB1 and target proteins, in this case, GST- A receptor molecule is said to exhibit cooperative binding if its binding to ligand scales nonlinearly with ligand concentration. Dec 30, 2015 · Cooperative binding is one of the most interesting and not fully understood phenomena involved in control and regulation of biological processes. In the case of positive cooperativity, the affinity of two concurrently bound agonists is greater than the affinity of a single bound agonist and the value of binding cooperativity factor α is higher than 1. Conversely, negative The sequential model aims to demonstrate cooperativity by assuming that the enzyme/protein molecule affinity is relative and changes as substrates bind. , sensitivity to substrate concentration and to affinity, as two manifestations of a single theory. Feb 16, 2024 · The cooperativity factor (α) and the intrinsic compound affinity to 14-3-3 (K DII) were determined by fitting, using a thermodynamic equilibrium model, which allows for an objective comparison of different stabilizers (Fig. was greater than 1 for both salivary and pancreatic α-amylases (Table 3). , FASEB J. negative cooperativity - -> if the ligand has different affinities for the protein binding sites (same or different protein) in solution, than nH will also be less than one. The cooperativity composite factor (Log αβ = 1. When appropriate, [clarification needed] the value of the Hill coefficient describes the cooperativity of ligand binding in the following way: n > 1 {\displaystyle n>1} . May 2, 2024 · Using 14-3-3/client complexes as examples, de Vink et al. 32 Fig. Sep 11, 2024 · The difference in the direction of G protein cooperativity between agonists and antagonists reflects a two-state model of allostery and allows for the comparison of cooperativity between the endogenous G protein and exogenous allosteric modulators. We developed fluorine NMR competition binding experiments to determine cooperativity of PROTACs. 3–5 The development of such cooperativity concepts is not only of relevance for so-called molecular glues2 and PROTACs,4 but Sep 11, 2024 · ‡Logarithm of the αβ cooperativity factor for the interaction between LY211 and ACh obtained from the operational model of allosterism. 2c). The concept of PROTAC cooperativity factor (α) was introduced in order to reflect the effects of protein-protein interactions (PPI) on ternary complex formation: α is mathematically defined as α = Kd (binary)/Kd (ternary) (Figure 3). We then quantified cooperativity underlying heterodimer-DNA binding and derived an integrative heterodimer DNA binding constant. The Cooperativity and Specificity section discusses cooperativity and specificity, e. Aug 29, 2015 · Cooperative binding has been described in many publications and has been related to or defined by several different properties of the binding behavior of the ligand to the target molecule. Binding of an allosteric agent may induce a shift alpha of the equilibrium dissociation constant K(D) of a radioligand for the orthosteric site. , 32. Mar 3, 2022 · In the presence of a prebound ligand the affinity of the coregulator for the receptor is altered by a cooperativity factor (α) to KID / α. The α -factor represents the effect of the ligand-induced conformational rearrangement of the receptor on coregulator apparent affinity. Here, we report that hydrogen peroxide or 3-morpholinosydnonimine, which simultaneously releases nitric oxide and superoxide, synergize with the cytokine tumor necrosis factor (TNF)-alpha to activate NF-kappaB in rat lung epithelial May 30, 2014 · The pioneer factor FOXA1 contributes to androgen receptor (AR)-dependent gene expression by opening chromatin to facilitate AR binding. e. Here the authors introduce a statistical Feb 6, 2017 · In analogy to the cooperativity factor in supramolecular polymerization, we can define the dimensionless ratio σ = k1 / k2 where a small value of σ (≪ 1) implies a highly cooperative reaction Rao et al. Recently determined structures have reveale … Mar 1, 2002 · Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo. , [22]). FOXA1 is not requ … Nov 6, 2020 · As such, α is considered a cooperativity factor by many in the field (19, 33). Jul 1, 2016 · Specificity and Subsite Cooperativity of Chlamydial Protease-like Activity Factor Chlamydial protease-like activity factor (CPAF, MEROPS ID S41. In this work, using the interaction energy of a molecular system, which is composed of multiple copies of a building block, we propose a quantitative measurement to evaluate the cooperativity Cooperativity as a concept is easy to grasp intuitively, but surprisingly hard to define. Likewise, the affinity of substrate (S) for E and for the enzyme–inhibitor (EI) complex will be affected by the same factor α, to form the thermodynamic cycle illustrated in Figure 1. Both dynamics cooperativity and the Hopfield-Ninio's kinetic proofreading mechanism for specificity amplification (24, 25) exhibit a square-law effect. Also, the typical low intrinsic affinity of small molecule stabilizers for either one of the individual protein partners limits facile detection or running of simple screening assays. , Dyson, H. Cooperative binding has been shown to be the mechanism underlying a large range of biochemical and physiological processes. Mar 1, 2002 · Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo Therefore we developed a system to compare the signal transducing capacities of dimers of Ig-alpha/Ig-alpha, Ig-beta/Ig-beta, or Ig-alpha/Ig-beta. (2002) Cooperativity in transcription factor binding to the coactivator CBP: The MLL activation domain binds to an allosteric site on the KIX domain. This review discusses the use of isothermal titration calorimetry (ITC) in the identification and characterisation of cooperativity in biological interactions. The cytoplasmic tails of each of these chains contain two conserved tyrosines, phosphorylation of which initiates the signal transduction cascades activated by the receptor complex. 4: Cooperativity. May 3, 2023 · When cooperativity is positive, the affinity of a vacant site is increased by occupancy of an adjacent one. May 21, 2025 · Heterotropic ligand binding to Diaphanous 1 leads to negative cooperativity as a key element in controlling Diaphanous 1 activity to enable gradual responses to cellular processes that require Oct 22, 2014 · Positive cooperativity refers to the fact that the binding of one substrate facilitates the binding of another substrate to the protein. The Hill coefficient, or , may describe cooperativity (or possibly other biochemical properties, depending on the context in which the Hill equation is being used). Auto-Inhibition of Ets-1 Is Counteracted by DNA Binding Cooperativity with Core-Binding Factor alpha 2 Ting-Lei Gu where E is the effect, [A] and [B] are the concentrations and K A, and K B are the equilibrium dissociation constants of the orthosteric and allosteric ligand, respectively, α is the cooperativity factor describing the allosteric effect of each ligand on the other’s binding affinity, β is a scaling factor (from zero to infinity) that There will be no need to introduce the cooperativity factor in this case, and the dose-response curve for the ternary complex strictly follows a sigmoidal saturation binding curve of a conventional binary binding system with an overall dissociation equilibrium constant of KPLE = KE1 × KP2. have described a cooperativity model 57 to quantify the efficacy of PPI stabilizers in terms of the cooperativity factor (α) between the stabilizer and the binding partners, as well as the intrinsic affinity of the stabilizer toward one of the apo-proteins (K DII) (Figure 3 B). Instead, cooperativity is driven by enhancer chromatin structure, pointing to how chromatin dynamics can regulate enhancer function. 5 - Diagram of tetrameric hemoglobin, showing statistical weights of different saturations (see text). 2003;17:1484–1507. ITC has broad scope in the analysis of cooperativity as it determines binding stiochiometries, affinities and thermodynamic parameters, including enthalpy and entropy in a single experiment Mar 1, 1996 · The B cell antigen receptor complex contains heterodimers of Ig-alpha and Ig-beta. For example, the enzyme may Figure 6. c) (7 points) L 2 binding to CGS 1 2 induces a conformational change that changes the KD for L I to 1 2 u M What is the cooperativity factor for this enzyme? Nov 14, 2024 · Furthermore, the thermodynamic cooperativity factor α, which defines the degree to which an inhibitor binding affects the affinity of the enzyme for the substrate, 29. Jul 13, 2023 · Positive cooperativity (α > 1) results from higher ternary complex binding affinity compared to corresponding binary complex due to favorable PPIs at the interface. Examine the different types of cooperativity and non-cooperativity, and discover an example of how cooperative It is characteristic of eukaryotic transcription that a unique combination of multiple transcriptional regulatory proteins bound to promoter DNA specifically activate or repress downstream target genes; this is referred to as combinatorial gene regulation. Although the cytoplasmic domains of … Is it appropriate to calculate a cooperativity factor using β derived from a two-site fit of ITC data? I am trying to assess whether my system is cooperative. Here we investigated the possible antineoplastic activities of alpha-TOH and alpha-TOS and further explored the potential of alpha-TOS as an antitumor agent Feb 1, 2023 · The time factor is present in an explicit way through the concept of residence time. Due to the scarcity Mar 7, 2022 · The large cooperativity observed led to a steep transition of the sigmoidal binding curve (Fig. Abstract The transcription factor nuclear factor (NF)-kappaB is activated by oxidative stress or cytokines and is critical to the activation of inflammatory genes. The increased throughput for the agonist shift assay is the first demonstration of allostery measurements on this scale, which were analyzed in an automated manner to produce quantifiable measurements of allostery: alpha (cooperativity factor), beta (efficacy), tauB (direct agonist activity of the allosteric ligand), and KB (intrinsic binding The factor of binding cooperativity α quantifies the change in agonist affinity upon binding of the second molecule of agonist to the dimer. In this work, we present a new computational framework to model the cooperativity between PROTAC–E3 binding and PROTAC–target binding principally through protein–protein interactions (PPIs) induced by the PROTAC. Here we analyze the simplest phenomenological model that can account for cooperativity (i. Jun 1, 2015 · FOXA1 (also known as hepatocyte nuclear factor 3α, or HNF-3α) is a protein of the FKHD family transcription factors. Apr 27, 2018 · Figure 7 Structural basis of AKG homotropic cooperativity in AnGDH. 16 If we define residence time as the time a ligand spends at the receptor-binding site, many different combinations of cooperativity rate constant values can be obtained from different ligands with similar equilibrium dissociation constants. If we consider that, in the absence of cooperative factors, optical activity is a short-range phenomenon, the contribution to the rotatory power of most parts of the chain is zero or near to zero. Cooperativity of co-factor NR2F2 with pioneer factors GATA3, FOXA1 in promoting ERα function. dat through Data_E. dat according to the operational model of allosterically modulated agonism (OMAMA) of various factors of binding cooperativity alpha with parameters in the header of the script. Jan 16, 2025 · From this, experimental conditions to determine the intrinsic cooperativity alpha with only one binding assay and without the need for a comprehensive mathematical model covering all simultaneous events under non-saturating conditions are highlighted. 2003-0020. , 15: 403-415, 2001). In this Kapp is the apparent KD and is made up of the KD of the radioligand modified by a factor consisting of modulator concentration, [ligand], the affinity cooperativity factor, α, and the dissociation constant of the modulator, KB. A cooperativity factor greater than 1 indicates positive cooperativity, where bound ligand increases the affinity for additional ligands, while a cooperativity factor less than one means that bound ligand reduces the affinity for additional ligands. Jun 20, 2024 · Using 14-3-3/client complexes as examples, de Vink et al. NR2F2 binding is very flexible to nuclear receptor motifs, and it can recognize the motif of other nuclear receptors (ERα, hepatocyte nuclear factor 4 alpha (HNF4A), thyroid receptor (TR), vitamin D receptor (VDR)); thus, it results in a competition for DNA binding sites between nuclear receptors [5]. J. Martinez-Yamout, M. 2: SAR around analog 1 results in improved stabilizer 30. A cooperativity framework to describe and interpret small-molecule stabilization of protein–protein interactions (PPI) is presented. Feb 28, 2021 · Jiang G, Wang X, Sheng D, Zhou L, Liu Y, Xu C, et al. Cooperativity is a phenomenon displayed by systems involving identical or near-identical elements, which act dependently of each other, relative to a hypothetical standard non-interacting system in which the individual elements are acting independently. Apr 7, 2021 · OMAMA_alpha_generate_5_data_sets. 46) was calculated using the operational model for agonism as described by Wootten et al. In that context, we develop methods for quantifying cooperativity by two ligands binding to distinct sites, first measuring individual binding constants and then a cooperativity factor (previously referred to as the cooperativity parameter in, e. FOXA1 has been termed as a pioneer transcription factor due to its unique ability of chromatin remodeling in which the chromatin can be de-compacted to allow genomic access by nuclear hormone receptors, including androgen receptor (AR) and estrogen receptor (ER). Theranostics. Description: Alpha factor which describes the cooperativity of binding of 2 identical inhibitor molecules. May 30, 2014 · The pioneer factor FOXA1 contributes to androgen receptor (AR)-dependent gene expression by opening chromatin to facilitate AR binding. Apr 27, 2018 · Positive cooperativity with Hill coefficients of up to 6 in the glutamate concentration dependence of steady-state reaction rates measured with clostridial glutamate dehydrogenase and the mutant A163G at high pH Two factors are critical for the sensitivity of Factor C to LPS: 1) the presence of multiple binding sites for LPS on a single Factor C molecule; and 2) high positive cooperativity in LPS binding. g. Using Jan 22, 2024 · Epigenomic, biochemical, structural, and human phenotypic analyses of transcription factors that regulate a composite DNA motif in the embryonic face and limb mesenchyme reveal how DNA-guided cooperative binding gives rise to specificity among members of large TF families. The correlated intrinsic affinities and the cooperativity factor in PPI-stabilization require to be determined with the support of a thermodynamic model. This was done by fusing the extracellular and transmembrane domains of either human platelet-derived growth factor receptor (PDGFR) alpha or beta to the cytoplasmic tail of either Ig-alpha or Ig-beta. uncover transcription factor binding and cooperativity at functional enhancers genome-wide in Drosophila cells. Two recent papers shed light on the issue and continue the debate on how best to define cooperative binding. Jul 16, 2018 · On the contrary, negative BTK–CRBN cooperativity is observed with PROTACs of shorter linkers, and relief of steric clashes is determined to describe the transition between ineffective and potent BTK degradation within this system. We show applicability to estimate both positive and Jul 10, 2017 · The intermolecular hydrogen-bonding interaction forms the central premise of this work, in which we evaluate the effect of different moieties such as alkyl chains, and amino acids, attached to the core amides on the strength of intermolecular HB, which consequently governs the extent of cooperativity (quantified by the cooperativity factor, σ). Nov 15, 2022 · In this work, we develop a pharmacodynamic model that describes the kinetics of the key reactions in the TPD process, and we use this model to investigate the role of cooperativity in the ternary complex formation and in the target POI degradation. Cooperative binding occurs in a Nov 18, 2021 · Introduction The rapidly increasing field of small molecule stabilization of Protein–Protein Interactions (PPIs)1,2 is intrinsically connected to molecular cooperativity mechanisms, because of the simultaneous interactions between more than two molecular entities. All BD1s also exhibited positive cooperativity, albeit to a much lesser extent (α between 2 and 3). Jul 18, 2022 · We call this cooperativity. Cooperative binding occurs in molecular binding systems containing more than one type, or species, of molecule and in which one of the partners is not mono-valent and can bind more than one molecule of the other species. A value of 1 indicates no cooperativity. 22 ,24 ,42 The cooperativity factor Alpha is defined by: Also, the typical low intrinsic affinity of small molecule stabilizers for either one of the individual protein partners limits facile detection or running of simple screening assays. Currently, the potency of PPI stabilizers is typically expressed by their apparent a ffi nity or EC50 Nov 1, 2017 · In that context, we develop methods for quantifying cooperativity by two ligands binding to distinct sites, first measuring individual binding constants and then a cooperativity factor (previously referred to as the cooperativity parameter in, e. 1210/me. Molecular glues and bivalent inducers of protein degradation (also known as PROTACs) represent a fascinating new modality in pharmacotherapeutics: the potential to knockdown previously thought ‘undruggable’ targets at sub-stoichiometric Jan 1, 2023 · The cooperativity factor (α = Kd binary /Kd ternary) provides a measure of susceptibility to ternary complex formation that represents the change in affinity factor between binary and ternary complexes. If n = 1, the Hill equation is reduced to its more familiar form known as the Michaelis-Menten equation. doi: 10. Using this cooperativity-inclusive constant, we were able to build a heterodimer-DNA binding specificity model that has superior predictive power than the one based on a regular one-site equilibrium. Jun 24, 2024 · This assay is used to determine the ternary complex affinity (KD,ternary value) and cooperativity factor alpha (α) of test compounds between His 6 -CRBN-DDB1 and target proteins, in this case, GST-BRD4 (BD1), GST-BRD4 (BD2), and His 6 -FKBP12. 2b, right panel), suggesting that the fitted Kd value could potentially be underestimating the real binding affinity of this ternary complex. show that because FOXA1 promotes AR Nov 21, 2023 · Learn what cooperative binding is. The maximal ternary complex formation increases with cooperativity and reaches saturation, after which it becomes independent of the cooperativity factor (Fig. Cooperative binding is most often observed in proteins, but nucleic acids can also exhibit cooperative binding, for instance of transcription factors. & Wright, P. Aug 21, 2019 · Estrogen receptor α (ERα) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcriptional events that promote tumor growth. We thus describe a case where robust thermodynamic cooperativity appears unnecessary for efficient degradation. To explore the role of cooperativity in HIF target selection, we integrated HIF1 alpha ChIP-chip binding locations across cell-types with a meta-analysis of gene expression profiles of cells exposed to hypoxia [13]. E. 1) 16. Sep 7, 2022 · An example of negative cooperativity is the decrease in binding affinity once one of the sites is bound. How FOXA1 controls the AR cistrome, however, is incompletely understood. ligand binding to a macromolecule with two binding sites) by generating equilibrium binding isotherms from deterministically simulated binding time courses Values of the factor of binding cooperativity α lower than 1 denote negative cooperativity, where binding of agonist and allosteric modulator mutually reduces the affinity of each other. Jun 21, 2024 · This assay is used to determine the ternary complex affinity (KD,ternary value) and cooperativity factor alpha (α) of test compounds between His 6 -CRBN-DDB1 and target proteins, in this case, GST-BRD4 (BD1), GST-BRD4 (BD2), and His 6 -FKBP12. et al. 8, 9 Cooperativity can be described as “positive” (α > 1, increased ternary binding affinity relative to the binary, further stabilizing Mar 2, 2025 · This resulted in small-molecule stabilizers with a cooperativity factor (α) up to 220 for the ChREBPα/14-3-3 PPI. Here we show that AR directly binds chromatin through the androgen response elements (AREs). ERα binding activity largely depends on access to binding sites on chromatin, which is facilitated in part by Pioneer Facto … Jan 8, 2020 · Although transcription factor (TF) cooperativity is widespread, a global mechanistic understanding of the role of TF cooperativity is still lacking. 011) is a serine protease secreted by the obligate intracellular pathogen Chlamydia trachomatis. ⁴⁵, with the slope constrained to 1. According to the cooperativity model, the K(A) of alloster binding is expected … Abstract Alpha-tocopheryl succinate (alpha-TOS), a redox-inactive analogue of vitamin E, is a strong inducer of apoptosis, whereas alpha-tocopherol (alpha-TOH) lacks apoptogenic activity (J. Cooperativity can be positive (if binding of a ligand molecule increases the receptor's apparent affinity, and hence increases the chance of another ligand molecule binding) or negative (if binding of a ligand molecule decreases affinity and hence makes binding of Mar 24, 2025 · These interactions lead to enhanced ligand binding—termed intrinsic cooperativity α—which can be retrieved via the apparent cooperativity either by monitoring ligand binding through the chaperone or through the target protein. Jan 16, 2025 · In this publication, the advantage of measuring the apparent cooperativity to determine the cooperativity alpha by the weaker binding protein is discussed and illustrated using the example of ternary complexes between FKBP12, MAPRE1 and macrocyclic molecular glues derived from the rapamycin binding motif for FKBP12. May 30, 2014 · The pioneering factor FOXA1 opens chromatin to facilitate androgen receptor (AR) binding to prostate-specific genes. §Negative logarithm of the allosteric modulator equilibrium dissociation constant (p KB) obtained from the operational model of allosterism. FOXA1 is not requ … Together, our results provide new mechanistic insight into REtr and c-KIT oncogenic cooperativity and suggest that augmented DNA repair accounts for the increased chemoresistance observed in t (8;21)-positive AML patients with activated c-KIT mutations. Neuzil et al. py generates 5 datasets named Data_A. Acta Biochim. p9cucuza u2u0 huwc0rg9q evkdg ijn zpv60v cdz vl6uw sl5goj enzf8mr

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