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AIMP2-DX2 provides therapeutic interface to control KRAS-driven tumorigenesis

Author

Listed:
  • Dae Gyu Kim

    (Yonsei University)

  • Yongseok Choi

    (Korea University)

  • Yuno Lee

    (Korea Research Institute of Chemical Technology)

  • Semi Lim

    (Yonsei University)

  • Jiwon Kong

    (Yonsei University)

  • JaeHa Song

    (Yonsei University)

  • Younah Roh

    (Yonsei University)

  • Dipesh S. Harmalkar

    (Korea University
    Dongguk University)

  • Kwanshik Lee

    (Korea University)

  • Ja-il Goo

    (Korea University)

  • Hye Young Cho

    (Korea University)

  • Ameeq Ul Mushtaq

    (Korea University)

  • Jihye Lee

    (Yonsei University)

  • Song Hwa Park

    (Yonsei University)

  • Doyeun Kim

    (Yonsei University)

  • Byung Soh Min

    (Yonsei University)

  • Kang Young Lee

    (Yonsei University)

  • Young Ho Jeon

    (Korea University)

  • Sunkyung Lee

    (Korea Research Institute of Chemical Technology)

  • Kyeong Lee

    (Dongguk University)

  • Sunghoon Kim

    (Yonsei University)

Abstract

Recent development of the chemical inhibitors specific to oncogenic KRAS (Kirsten Rat Sarcoma 2 Viral Oncogene Homolog) mutants revives much interest to control KRAS-driven cancers. Here, we report that AIMP2-DX2, a variant of the tumor suppressor AIMP2 (aminoacyl-tRNA synthetase-interacting multi-functional protein 2), acts as a cancer-specific regulator of KRAS stability, augmenting KRAS-driven tumorigenesis. AIMP2-DX2 specifically binds to the hypervariable region and G-domain of KRAS in the cytosol prior to farnesylation. Then, AIMP2-DX2 competitively blocks the access of Smurf2 (SMAD Ubiquitination Regulatory Factor 2) to KRAS, thus preventing ubiquitin-mediated degradation. Moreover, AIMP2-DX2 levels are positively correlated with KRAS levels in colon and lung cancer cell lines and tissues. We also identified a small molecule that specifically bound to the KRAS-binding region of AIMP2-DX2 and inhibited the interaction between these two factors. Treatment with this compound reduces the cellular levels of KRAS, leading to the suppression of KRAS-dependent cancer cell growth in vitro and in vivo. These results suggest the interface of AIMP2-DX2 and KRAS as a route to control KRAS-driven cancers.

Suggested Citation

  • Dae Gyu Kim & Yongseok Choi & Yuno Lee & Semi Lim & Jiwon Kong & JaeHa Song & Younah Roh & Dipesh S. Harmalkar & Kwanshik Lee & Ja-il Goo & Hye Young Cho & Ameeq Ul Mushtaq & Jihye Lee & Song Hwa Park, 2022. "AIMP2-DX2 provides therapeutic interface to control KRAS-driven tumorigenesis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30149-2
    DOI: 10.1038/s41467-022-30149-2
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    References listed on IDEAS

    as
    1. Jude Canon & Karen Rex & Anne Y. Saiki & Christopher Mohr & Keegan Cooke & Dhanashri Bagal & Kevin Gaida & Tyler Holt & Charles G. Knutson & Neelima Koppada & Brian A. Lanman & Jonathan Werner & Aaron, 2019. "The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity," Nature, Nature, vol. 575(7781), pages 217-223, November.
    2. Tsang, Eric W. K., 2014. "Old and New," Management and Organization Review, Cambridge University Press, vol. 10(03), pages 390-390, November.
    3. Gideon Bollag & Chao Zhang, 2013. "Pocket of opportunity," Nature, Nature, vol. 503(7477), pages 475-476, November.
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