Daning Lu

Sun Yat-sen Memorial Hospital

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Kaishun Hu

Sun Yat-sen Memorial Hospital

Limin Xie

Sun Yat-sen Memorial Hospital

Wenjing Wu

Sun Yat-sen Memorial Hospital

Lehang Lin

Sun Yat-sen Memorial Hospital

Yin Zhang

Sun Yat-sen University

H. Phillip Koeffler

Cedars-Sinai Medical Center

Jingyuan Zhang

Sun Yat-sen Memorial Hospital

Jiehua He

Sun Yat-sen Memorial Hospital

Dong Yin

Sun Yat-sen Memorial Hospital

Yu Li

Peking University Shenzhen Hospital

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Sun Yat-sen Memorial Hospital

Sun Yat-sen University

Sun Yat-sen University Cancer Center

Nanjing University of Science and Technology

Key Laboratory of Guangdong Province

Synopsys (Switzerland)

Dongguan University of Technology

Southern Medical University

National Taiwan University

Cedars-Sinai Medical Center

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

International Journal of Biological Sciences (2024)

Kaishun Hu Limin Xie Wenjing Wu Jingyuan Zhang Yu Li

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.

PLK1

CYR61

10.7150/ijbs.93335

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