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Creatine kinase in cell cycle regulation and cancer

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Abstract

The phosphocreatine-creatine kinase (CK) shuttle system is increasingly recognized as a fundamental mechanism for ATP homeostasis in both excitable and non-excitable cells. Many intracellular processes are ATP dependent. Cell division is a process requiring a rapid rate of energy turnover. Cell cycle regulation is also a key point to understanding the mechanisms underlying cancer progression. It has been known for about 40 years that aberrant CK levels are associated with various cancers and for over 30 years that CK is involved in mitosis regulation. However, the underlying molecular mechanisms have not been investigated sufficiently until recently. By maintaining ATP at sites of high-energy demand, CK can regulate cell cycle progression by affecting the intracellular energy status as well as by influencing signaling pathways that are essential to activate cell division and cytoskeleton reorganization. Aberrant CK levels may impair cell viability under normal or stressed conditions and induce cell death. The involvement of CK in cell cycle regulation and cellular energy metabolism makes it a potential diagnostic biomarker and therapeutic target in cancer. To understand the multiple physiological/pathological functions of CK, it is necessary to identify CK-binding partners and regulators including proteins, non-coding RNAs and participating endogenous small molecular weight chemical compounds. This review will focus on molecular mechanisms of CK in cell cycle regulation and cancer progression. It will also discuss the implications of recent mechanistic studies, the emerging problems and future challenges of the multifunctional enzyme CK.

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Acknowledgments

The author thanks Dr. T Wallimann, Dr. R Harris and Prof. HP Gong for critical reading and helpful suggestions, Dr. H-M Zhou for 10 year’s collaboration into CK folding and function, and all former and present laboratory members involved in CK projects. The various CK projects undertaken in the author’s laboratory were supported by Grants 2012CB917304 and 2010CB912402 from the Ministry of Science and Technology of China, Grants 30500084 and 30970559 from the National Natural Science Foundation of China and support from State Key Laboratory of Membrane Biology.

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  1. State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China

    Yong-Bin Yan

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Yan, YB. Creatine kinase in cell cycle regulation and cancer. Amino Acids 48, 1775–1784 (2016). https://doi.org/10.1007/s00726-016-2217-0

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