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Role of MARK2 in the nervous system and cancer

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Abstract

Microtubule-Affinity Regulating Kinase 2 (MARK2), a member of the serine/threonine protein kinase family, phosphorylates microtubule-associated proteins, playing a crucial role in cancer and neurodegenerative diseases. This kinase regulates multiple signaling pathways, including the WNT, PI3K/AKT/mTOR (PAM), and NF-κB pathways, potentially linking it to cancer and the nervous system. As a crucial regulator of the PI3K/AKT/mTOR pathway, the loss of MARK2 inhibits the growth and metastasis of cancer cells. MARK2 is involved in the excessive phosphorylation of tau, thus influencing neurodegeneration. Therefore, MARK2 emerges as a promising drug target for the treatment of cancer and neurodegenerative diseases. Despite its significance, the development of inhibitors for MARK2 remains limited. In this review, we aim to present detailed information on the structural features of MARK2 and its role in various signaling pathways associated with cancer and neurodegenerative diseases. Additionally, we further characterize the therapeutic potential of MARK2 in neurodegenerative diseases and cancer, and hope to facilitate basic research on MARK2 and the development of inhibitors targeting MARK2.

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Fig. 1: MARK2 gene changes in cancer.
Fig. 2: 2D and 3D structure of MARK2.
Fig. 3
Fig. 4

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Data availability

Data will be made available on request.

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Acknowledgements

This work was supported by grants from Hubei University of Science and Technology (2021WG01; 2022TNB02) to FC, and Department of Education of Hubei Province (T201921) to FC, and Natural Science Foundation of Hubei Province (2023AFD111) to FC.

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Authors and Affiliations

  1. School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, China

    Yining Lei

  2. Hubei Key Laboratory of Diabetes and Angiopathy, Hubei University of Science and Technology, Xianning, 437100, China

    Yining Lei, Ruyi Zhang & Fei Cai

  3. School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, China

    Fei Cai

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  1. Yining Lei
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  3. Fei Cai
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YL: writing – original draft; RZ: methodology; FC: writing – original draft, funding acquisition.

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Lei, Y., Zhang, R. & Cai, F. Role of MARK2 in the nervous system and cancer. Cancer Gene Ther 31, 497–506 (2024). https://doi.org/10.1038/s41417-024-00737-z

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