Transcription factor complex (TFC)

Transcription factor complexes are multi-protein assemblies that regulate gene expression by binding to specific DNA sequences, thereby controlling the recruitment of RNA polymerase [1]. These complexes typically consist of sequence-specific DNA-binding proteins, co-activators or co-repressors, and chromatin-remodeling factors that integrate various cellular signals to execute precise transcriptional programs [2]. Dysregulation of these complexes is central to the pathogenesis of many diseases; for instance, the constitutive activation of the NF-kappaB or STAT3 complexes is a driver in many cancers and inflammatory conditions [3]. Historically, these complexes were considered difficult to target with small molecules because they lack deep, hydrophobic pockets and rely on large-surface-area interactions [4]. However, modern therapeutic approaches have successfully targeted them through various means, including the use of nuclear receptor modulators, inhibitors of protein-protein interactions, and molecular glues that induce the degradation of specific transcription factor subunits [5]. Sources: [1] Lambert et al. (2018) Cell 172(4):650-665; [2] Bushweller (2019) Nat Rev Cancer 19(3):163-178; [3] Bhagwat & Vakoc (2015) Trends Cancer 1(1):52-65; [4] Yan & Higgins (2013) J Cancer 3(1):1-10; [5] Koehler (2010) Curr Opin Chem Biol 14(3):331-340.

Other names

Transcriptional complexDNA-binding protein complexTranscriptional machineryTranscription factor assembly

Inhibition of DNA binding, disruption of protein-protein interactions, modulation of co-activator/co-repressor recruitment, and targeted protein degradation.