Lenalidomide: deciphering mechanisms of action in myeloma, myelodysplastic syndrome and beyond.

Curr Opin Cell Biol
Authors
Andrew Guirguis
Benjamin Ebert
Keywords
Animals
Humans
Ubiquitination
Transcription, Genetic
Substrate Specificity
Multiple Myeloma
Thalidomide
Myelodysplastic Syndromes
Angiogenesis Inhibitors
Abstract

Lenalidomide and its related 'analogues' modulate the substrate specificity of the CRL4(CRBN) E3 ubiquitin ligase complex. Polyubiquitination and subsequent proteasomal degradation of IKZF1 and IKZF3 in multiple myeloma and CK1α 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.
Year of Publication
2015
Journal
Curr Opin Cell Biol
Volume
37
Pages
61-7
Date Published
2015 Dec
ISSN
1879-0410
URL
http://linkinghub.elsevier.com/retrieve/pii/S0955-0674(15)00118-0
DOI
10.1016/j.ceb.2015.10.004
PubMed ID
26512454
Links
Grant list
P01 CA108631 / CA / NCI NIH HHS / United States
R01HL082945 / HL / NHLBI NIH HHS / United States

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