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Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase

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  • Georg Petzold

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Eric S. Fischer

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel
    †Present addresses: Department of Cancer Biology, Dana-Farber Cancer Institute, LC-4312, 360 Longwood Avenue, Boston, Massachusetts 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02215, USA.)

  • Nicolas H. Thomä

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

Abstract

Thalidomide and its derivative lenalidomide bind the CRL4CRBN E3 ubiquitin ligase and target protein substrates for degradation; structural and functional data determined here show that casein kinase 1α and the lymphoid transcription factor Ikaros, the efficacy targets of lenalidomide in two different blood cancers, interact with the CRBN–lenalidomide interface through a β-hairpin destruction motif.

Suggested Citation

  • Georg Petzold & Eric S. Fischer & Nicolas H. Thomä, 2016. "Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase," Nature, Nature, vol. 532(7597), pages 127-130, April.
    • Handle: RePEc:nat:nature:v:532:y:2016:i:7597:d:10.1038_nature16979
    DOI: 10.1038/nature16979
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    Cited by:

    1. Olena S. Tokareva & Kunhua Li & Tara L. Travaline & Ty M. Thomson & Jean-Marie Swiecicki & Mahmoud Moussa & Jessica D. Ramirez & Sean Litchman & Gregory L. Verdine & John H. McGee, 2023. "Recognition and reprogramming of E3 ubiquitin ligase surfaces by α-helical peptides," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Gisele Nishiguchi & Lauren G. Mascibroda & Sarah M. Young & Elizabeth A. Caine & Sherif Abdelhamed & Jeffrey J. Kooijman & Darcie J. Miller & Sourav Das & Kevin McGowan & Anand Mayasundari & Zhe Shi &, 2024. "Selective CK1α degraders exert antiproliferative activity against a broad range of human cancer cell lines," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Dongwen Lv & Pratik Pal & Xingui Liu & Yannan Jia & Dinesh Thummuri & Peiyi Zhang & Wanyi Hu & Jing Pei & Qi Zhang & Shuo Zhou & Sajid Khan & Xuan Zhang & Nan Hua & Qingping Yang & Sebastian Arango & , 2021. "Development of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    4. Alena Kroupova & Valentina A. Spiteri & Zoe J. Rutter & Hirotake Furihata & Darren Darren & Sarath Ramachandran & Sohini Chakraborti & Kevin Haubrich & Julie Pethe & Denzel Gonzales & Andre J. Wijaya , 2024. "Design of a Cereblon construct for crystallographic and biophysical studies of protein degraders," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Meropi Bagka & Hyeonyi Choi & Margaux Héritier & Hanna Schwaemmle & Quentin T. L. Pasquer & Simon M. G. Braun & Leonardo Scapozza & Yibo Wu & Sascha Hoogendoorn, 2023. "Targeted protein degradation reveals BET bromodomains as the cellular target of Hedgehog pathway inhibitor-1," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Satoshi Yamanaka & Hirotake Furihata & Yuta Yanagihara & Akihito Taya & Takato Nagasaka & Mai Usui & Koya Nagaoka & Yuki Shoya & Kohei Nishino & Shuhei Yoshida & Hidetaka Kosako & Masaru Tanokura & Ta, 2023. "Lenalidomide derivatives and proteolysis-targeting chimeras for controlling neosubstrate degradation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Jean M. Etersque & Iris K. Lee & Nitika Sharma & Kexiang Xu & Andrew Ruff & Justin D. Northrup & Swarbhanu Sarkar & Tommy Nguyen & Richard Lauman & George M. Burslem & Mark A. Sellmyer, 2023. "Regulation of eDHFR-tagged proteins with trimethoprim PROTACs," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Shiyun Cao & Shoukai Kang & Haibin Mao & Jiayu Yao & Liangcai Gu & Ning Zheng, 2022. "Defining molecular glues with a dual-nanobody cannabidiol sensor," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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