Overlapping characteristics of weak interactions of two transcriptional regulators with WDR5

Ahmad, Mohammad; Imran, Ali; Movileanu, Liviu

doi:10.1016/j.ijbiomac.2023.128969

Cited by 1 publication

(3 citation statements)

References 71 publications

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“…89,90 For example, MYC regulates essential processes of gene transcription, such as epigenetic modifications, as well as promoter binding, initiation, elongation, and posttranscriptional events. Using different approaches, we 4 and others 6 found that MYC WBM weakly interacts with WDR5. One immediate question is whether the full-length MYC also exhibits a weak affinity against the full-length WDR5.…”

Section: Comparisons Between Myc W B M −Wdr5 and Mll4mentioning

confidence: 97%

“…One immediate question is whether the full-length MYC also exhibits a weak affinity against the full-length WDR5. In an independently executed fluorescence resonance energy transfer (FRET) study in living cells, 4 a weak MYC-WDR5 interaction was confirmed through a low FRET efficiency of the complex formation. MYC recruitment to chromatin is facilitated by its coordinated interactions with an obligate MAX binding partner, a specific E-box DNA sequence, and a prebound WDR5 molecule.…”

Section: Comparisons Between Myc W B M −Wdr5 and Mll4mentioning

confidence: 99%

“…Transcription factors (TFs) are essential members of the human proteome with the primary mission of regulating gene expression . Their interactions with deoxyribonucleic acid (DNA) regions and other protein coregulators mediate this critical function. − In addition, TFs control disease development, so their interfaces with protein cofactors are potentially pursued as essential therapeutic targets. For example, c-myelocytomatosis (MYC), an oncoprotein TF, uses the druggable WD r epeat-containing protein 5 (WDR5) as a cofactor. − MYC is overexpressed in 70% of human cancers and controls genes that influence cell development and apoptosis. − Experimental evidence indicated that MYC interacts with WDR5, , utilizing one of its intrinsically disordered regions and the W DR5 b inding m otif (WBM) site .…”

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confidence: 99%

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Real-Time Measurement of a Weak Interaction of a Transcription Factor Motif with a Protein Hub at Single-Molecule Precision

Mayse,

Wang,

Ahmad

et al. 2024

ACS Nano

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Transcription factors often interact with other protein cofactors, regulating gene expression. Direct detection of these brief events using existing technologies remains challenging due to their transient nature. In addition, intrinsically disordered domains, intranuclear location, and lack of cofactor-dependent active sites of transcription factors further complicate the quantitative analysis of these critical processes. Here, we create a genetically encoded label-free sensor to identify the interaction between a motif of the MYC transcription factor, a primary cancer driver, and WDR5, a chromatin-associated protein hub. Using an engineered nanopore equipped with this motif, WDR5 is probed through reversible captures and releases in a one-by-one and timeresolved fashion. Our single-molecule kinetic measurements indicate a weak-affinity interaction arising from a relatively slow complex association and a fast dissociation of WDR5 from the tethered motif. Further, we validate this subtle interaction by determinations in an ensemble using single nanodisc-wrapped nanopores immobilized on a biolayer interferometry sensor. This study also provides the proof-of-concept for a sensor that reveals unique recognition signatures of different protein binding sites. Our foundational work may be further developed to produce sensing elements for analytical proteomics and cancer nanomedicine.

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Section: Comparisons Between Myc W B M −Wdr5 and Mll4mentioning

confidence: 97%

Section: Comparisons Between Myc W B M −Wdr5 and Mll4mentioning

confidence: 99%