Affiliation:
1. Brigham and Women’s Hospital, Division of Hematology, Boston, MA
Abstract
Abstract
Lenalidomide acts by a novel drug mechanism—modulation of the substrate specificity of the CRL4CRBN E3 ubiquitin ligase. In multiple myeloma, lenalidomide induces the ubiquitination of IKZF1 and IKZF3 by CRL4CRBN. Subsequent proteasomal degradation of these transcription factors kills multiple myeloma cells. In del(5q) myelodysplastic syndrome, lenalidomide induces the degradation of CK1α, which preferentially affects del(5q) cells because they express this gene at haploinsufficient levels. In the future, modulation of ubiquitin ligase function may enable us to target previously “undruggable” proteins.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
137 articles.
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