CYR61 Acts as an Intracellular Microtubule-Associated Protein and Coordinates Mitotic Progression via PLK1-FBW7 Pathway

Hu, Kaishun; Xie, Limin; Wu, Wenjing; Zhang, Jingyuan; Li, Yu; He, Jiehua; Zhang, Yin; Lu, Daning; Koeffler, H. Phillip; Lin, Lehang; Yin, Dong

doi:10.7150/ijbs.93335

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Int J Biol Sci 2024; 20(8):3140-3155. doi:10.7150/ijbs.93335 This issue Cite

Research Paper

CYR61 Acts as an Intracellular Microtubule-Associated Protein and Coordinates Mitotic Progression via PLK1-FBW7 Pathway

Kaishun Hu^1*, Limin Xie^1*, Wenjing Wu^1,2*, Jingyuan Zhang¹, Yu Li³, Jiehua He¹, Yin Zhang¹, Daning Lu¹, H. Phillip Koeffler^4,5, Lehang Lin^1✉, Dong Yin^1✉

1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.
2. Department of Breast Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.
3. Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen 518000, P.R. China.
4. Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore.
5. Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
* These authors contributed equally to the paper as first authors.

Citation:

Hu K, Xie L, Wu W, Zhang J, Li Y, He J, Zhang Y, Lu D, Koeffler HP, Lin L, Yin D. CYR61 Acts as an Intracellular Microtubule-Associated Protein and Coordinates Mitotic Progression via PLK1-FBW7 Pathway. Int J Biol Sci 2024; 20(8):3140-3155. doi:10.7150/ijbs.93335. https://www.ijbs.com/v20p3140.htm

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Abstract

Cysteine-rich angiogenic inducer 61 (CYR61), also called CCN1, has long been characterized as a secretory protein. Nevertheless, the intracellular function of CYR61 remains unclear. Here, we found that CYR61 is important for proper cell cycle progression. Specifically, CYR61 interacts with microtubules and promotes microtubule polymerization to ensure mitotic entry. Moreover, CYR61 interacts with PLK1 and accumulates during the mitotic process, followed by degradation as mitosis concludes. The proteolysis of CYR61 requires the PLK1 kinase activity, which directly phosphorylates two conserved motifs on CYR61, enhancing its interaction with the SCF E3 complex subunit FBW7 and mediating its degradation by the proteasome. Mutations of phosphorylation sites of Ser167 and Ser188 greatly increase CYR61's stability, while deletion of CYR61 extends prophase and metaphase and delays anaphase onset. In summary, our findings highlight the precise control of the intracellular CYR61 by the PLK1-FBW7 pathway, accentuating its significance as a microtubule-associated protein during mitotic progression.

Keywords: CYR61, PLK1, mitosis, microtubules, FBW7

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APA

Hu, K., Xie, L., Wu, W., Zhang, J., Li, Y., He, J., Zhang, Y., Lu, D., Koeffler, H.P., Lin, L., Yin, D. (2024). CYR61 Acts as an Intracellular Microtubule-Associated Protein and Coordinates Mitotic Progression via PLK1-FBW7 Pathway. International Journal of Biological Sciences, 20(8), 3140-3155. https://doi.org/10.7150/ijbs.93335.

ACS

Hu, K.; Xie, L.; Wu, W.; Zhang, J.; Li, Y.; He, J.; Zhang, Y.; Lu, D.; Koeffler, H.P.; Lin, L.; Yin, D. CYR61 Acts as an Intracellular Microtubule-Associated Protein and Coordinates Mitotic Progression via PLK1-FBW7 Pathway. Int. J. Biol. Sci. 2024, 20 (8), 3140-3155. DOI: 10.7150/ijbs.93335.

NLM

CSE

Hu K, Xie L, Wu W, Zhang J, Li Y, He J, Zhang Y, Lu D, Koeffler HP, Lin L, Yin D. 2024. CYR61 Acts as an Intracellular Microtubule-Associated Protein and Coordinates Mitotic Progression via PLK1-FBW7 Pathway. Int J Biol Sci. 20(8):3140-3155.

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