Myc proto-oncogene protein nuclear condensate (MYC nuclear condensate) (MYC condensate)

Myc proto-oncogene protein (MYC) nuclear condensates are membraneless organelles formed through liquid-liquid phase separation (LLPS), a process primarily driven by the intrinsically disordered regions (IDRs) of the MYC protein (Boija et al., Cell, 2018). These condensates function as transcriptional hubs that concentrate MYC, its obligate partner MAX, and essential co-activators such as MED1 and BRD4 at specific genomic loci to drive high-level gene expression (Sabari et al., Science, 2018). By compartmentalizing the transcriptional machinery, these assemblies facilitate the high-level gene expression required for rapid cell growth and metabolic adaptation. In many human cancers, MYC is overexpressed or dysregulated, leading to the formation of enlarged, aberrant condensates that drive oncogenic programs (Covic et al., Nature Communications, 2023). Although MYC has historically been considered "undruggable" due to its lack of a stable globular structure, targeting the physical properties and assembly of these condensates offers a novel therapeutic avenue. Current approaches include the use of mini-proteins like Omomyc (OMO-103), small-molecule inhibitors of MYC-MAX interaction, and emerging condensate-modifying drugs (c-mods) designed to dissolve or alter these hubs (Duffy et al., Trends in Cancer, 2021). These strategies aim to selectively disrupt oncogenic transcription while minimizing the systemic toxicity associated with broad MYC inhibition (Soucek et al., Nature, 2008).

Other names

MYC biomolecular condensateMYC transcriptional condensateMYC-MAX condensateMYC-containing phase-separated assemblyc-Myc nuclear condensate

Disruption of MYC-MAX dimerization, inhibition of liquid-liquid phase separation (LLPS), proteasomal degradation of MYC, and interference with transcriptional co-activator recruitment.