Lenalidomide induces ubiquitination and degradation of casein kinase 1A1 in del(5q) MDS
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: Steven A. Carr
PROVIDER: MSV000079014 | MassIVE | Mon Jan 26 06:47:00 GMT 2015
REPOSITORIES: MassIVE
Publications
Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS.
Krönke Jan J Fink Emma C EC Hollenbach Paul W PW MacBeth Kyle J KJ Hurst Slater N SN Udeshi Namrata D ND Chamberlain Philip P PP Mani D R DR Man Hon Wah HW Gandhi Anita K AK Svinkina Tanya T Schneider Rebekka K RK McConkey Marie M Järås Marcus M Griffiths Elizabeth E Wetzler Meir M Bullinger Lars L Cathers Brian E BE Carr Steven A SA Chopra Rajesh R Ebert Benjamin L BL
Nature 20150701 7559
Lenalidomide is a highly effective treatment for myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)). Here, we demonstrate that lenalidomide induces the ubiquitination of casein kinase 1A1 (CK1α) by the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4(CRBN)), resulting in CK1α degradation. CK1α is encoded by a gene within the common deleted region for del(5q) MDS and haploinsufficient expression sensitizes cells to lenalidomide therapy, providing a mechanistic basis for ...[more]
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