Myc proto-oncogene protein-containing transcriptional condensate (MYC condensate) (MYC condensate)

Myc proto-oncogene protein-containing transcriptional condensates are specialized biomolecular assemblies formed through liquid-liquid phase separation (LLPS) that concentrate the MYC oncoprotein, its obligate partner MAX, and various transcriptional co-activators like MED1 and BRD4 at genomic loci, particularly super-enhancers (Boija et al., Cell, 2018; Sabari et al., Science, 2018). These condensates function as high-efficiency hubs that compartmentalize and concentrate the transcriptional machinery, thereby driving the massive up-regulation of genes involved in cell growth, metabolism, and proliferation (Dang, Cell, 2012). In many human cancers, the dysregulation of MYC leads to the aberrant formation or expansion of these condensates, which sustains the oncogenic state. Historically considered undruggable due to the lack of stable binding pockets in MYC's intrinsically disordered regions, these condensates now represent a promising therapeutic target (Klein et al., Science, 2020). Current pharmacological strategies focus on disrupting the physical properties of these droplets or using small molecules and PROTACs to destabilize the protein interactions required for their formation. This approach represents a shift from targeting individual protein structures to targeting the collective behavior of oncogenic protein assemblies.

Other names

MYC transcriptional condensateMYC-MAX condensateMYC-driven biomolecular condensateMYC-associated phase-separated condensate

Disruption of liquid-liquid phase separation (LLPS), inhibition of MYC-MAX dimerization, and targeted degradation of MYC or its co-activators to prevent the assembly of transcriptional hubs (Boija et al., Cell, 2018; Klein et al., Science, 2020).