CRISPRing the CRL4CRBN RING in multiple myeloma

Abstract

In this issue of Blood, Sievers et al describe key proteins required for the anti–myeloma properties of lenalidomide. By performing CRISPR-Cas9 functional genetic screening, they identify 2 E2 ubiquitin-conjugating enzymes (UBE2D3 and UBE2G1) and the COP9 signalosome as essential for lenalidomide-dependent CRL4CRBN function in myeloma due to their regulation of CRL4CRBN activity and ubiquitination of target substrates.1