Dataset Information

Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells

ABSTRACT: Data from Massive, ID: MSV000079017. Experiment: KGG, Rep2, file: G20121009_NU_Ebert_KGG_L-1uMLen_M-No_H-20uMThal_Rep02_bRPFxn06.mzml. Published as part of Science. 2014 Jan 17;343(6168):301-5 . From the Abstract: {{i}} Lenalidomide is a drug with clinical efficacy in multiple myeloma and other B cell neoplasms, but its mechanism of action is unknown. Using quantitative proteomics, we found that lenalidomide causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. IKZF1 and IKZF3 are essential transcription factors in multiple myeloma. A single amino acid substitution of IKZF3 conferred resistance to lenalidomide-induced degradation and rescued lenalidomide-induced inhibition of cell growth. Similarly, we found that lenalidomide-induced interleukin-2 production in T cells is due to depletion of IKZF1 and IKZF3 ... {{/i}}

INSTRUMENT(S): Instrument

ORGANISM(S): Homo_sapiens_viruses, Human

DISEASE(S): Not Available

SUBMITTER: Kroenke J, et al.

PROVIDER: GPM32310006306 | GPMDB |

REPOSITORIES: GPMDB

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Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells.

Krönke Jan J Udeshi Namrata D ND Narla Anupama A Grauman Peter P Hurst Slater N SN McConkey Marie M Svinkina Tanya T Heckl Dirk D Comer Eamon E Li Xiaoyu X Ciarlo Christie C Hartman Emily E Munshi Nikhil N Schenone Monica M Schreiber Stuart L SL Carr Steven A SA Ebert Benjamin L BL

Science (New York, N.Y.) 20131129 6168

Lenalidomide is a drug with clinical efficacy in multiple myeloma and other B cell neoplasms, but its mechanism of action is unknown. Using quantitative proteomics, we found that lenalidomide causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. IKZF1 and IKZF3 are essential transcription factors in multiple myeloma. A single amino acid substitution of IKZF3 conferred resistance to lenalidomide-induced degradati ...[more]

PMID: 24292625

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Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells

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Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells.

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