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Copper is essential for cyclin B1-mediated CDK1 activation

Author

Listed:
  • Jiaru Wang

    (Northeast Forestry University)

  • Dian Yang

    (Northeast Forestry University)

  • Hai-Fan Yu

    (Northeast Forestry University)

  • Jing Jin

    (Northeast Forestry University)

  • Yuzhe Nie

    (Northeast Forestry University)

  • Sihua Zhang

    (Northeast Forestry University)

  • Weiwei Ren

    (Shanghai Normal University)

  • Zihan Ge

    (Northeast Forestry University)

  • Zhuo Zhang

    (Northeast Forestry University)

  • Xinghong Ma

    (Northeast Agricultural University)

  • Shaojun Dai

    (Shanghai Normal University)

  • Guangchao Sui

    (Northeast Forestry University)

  • Chun-Bo Teng

    (Northeast Forestry University)

Abstract

Cyclin-dependent kinase 1 (CDK1) is the pivotal kinase responsible for initiating cell division. Its activation is dependent on binding to regulatory cyclins, such as CCNB1. Our research demonstrates that copper binding to both CDK1 and CCNB1 is essential for activating CDK1 in cells. Mutations in the copper-binding amino acids of either CDK1 or CCNB1 do not disrupt their interaction but are unable to activate CDK1. We also reveal that CCNB1 facilitates the transfer of copper from ATOX1 to CDK1, consequently activating its kinase function. Disruption of copper transfer through the ATOX1-CCNB1-CDK1 pathway can impede CDK1 activation and halt cell cycle progression. In summary, our findings elucidate a mechanism through which copper promotes CDK1 activation and the G2/M transition in the cell cycle. These results could provide insight into the acquisition of proliferative properties associated with increased copper levels in cancer and offer targets for cancer therapy.

Suggested Citation

  • Jiaru Wang & Dian Yang & Hai-Fan Yu & Jing Jin & Yuzhe Nie & Sihua Zhang & Weiwei Ren & Zihan Ge & Zhuo Zhang & Xinghong Ma & Shaojun Dai & Guangchao Sui & Chun-Bo Teng, 2025. "Copper is essential for cyclin B1-mediated CDK1 activation," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57538-7
    DOI: 10.1038/s41467-025-57538-7
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    References listed on IDEAS

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    1. Nicholas R. Brown & Svitlana Korolchuk & Mathew P. Martin & Will A. Stanley & Rouslan Moukhametzianov & Martin E. M. Noble & Jane A. Endicott, 2015. "CDK1 structures reveal conserved and unique features of the essential cell cycle CDK," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    2. Donita C. Brady & Matthew S. Crowe & Michelle L. Turski & G. Aaron Hobbs & Xiaojie Yao & Apirat Chaikuad & Stefan Knapp & Kunhong Xiao & Sharon L. Campbell & Dennis J. Thiele & Christopher M. Counter, 2014. "Copper is required for oncogenic BRAF signalling and tumorigenesis," Nature, Nature, vol. 509(7501), pages 492-496, May.
    Full references (including those not matched with items on IDEAS)

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