Journal
CURRENT OPINION IN CELL BIOLOGY
Volume 37, Issue -, Pages 61-67Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.ceb.2015.10.004
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Funding
- NIH [R01HL082945, P01 CA108631]
- Leukemia and Lymphoma Society Scholar Award
- Haematology Society of Australia and New Zealand New Investigator Scholarship
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Lenalidomide and its related 'analogues' modulate the substrate specificity of the CRL4CRBN E3 ubiquitin ligase complex. Polyubiquitination and subsequent proteasomal degradation of IKZF1 and IKZF3 in multiple myeloma and CK1 alpha in del(5q) MDS has recently been linked to therapeutic efficacy of this class of compounds. Harnessing ubiquitin ligase substrate specificity, may in time facilitate the degradation of other 'undruggable' proteins and allow for separation of detrimental side effects of IMiD compounds from those associated with therapeutic efficacy.
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