13Mar 2023
Ubiquitination Regulation of EZH2 in Melanoma

Ubiquitination Regulation of EZH2 in Melanoma

This study identified melanin pigment content as a primary source of cellular heterogeneity in melanoma and compared RNAseq data from high-pigmented (HPCs) and low-pigmented melanoma cells (LPCs), suggesting EZH2 as a master regulator of these states. EZH2 protein was upregulated in LPCs and inversely correlated with melanin deposition in pigmented patient melanomas. Surprisingly, conventional EZH2 methyltransferase inhibitors, GSK126 and EPZ6438, did not affect LPC survival, clonogenicity and pigmentation, despite fully inhibiting methyltransferase activity. Targeting UHRF1/UBE2L6/UBR4-mediated regulation of EZH2 offers the potential for modulating the exercise of this oncoprotein in contexts in which conventional EZH2 methyltransferase inhibitors are ineffective.

  • #oncology

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