PDF(Pubmed)
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.
摘要：
富含半胱氨酸的血管生成诱导剂61(CYR61),也称为CCN1，长期以来一直被表征为分泌蛋白。然而，CYR61的细胞内功能尚不清楚。这里,我们发现CYR61对于正确的细胞周期进程很重要.具体来说,CYR61与微管相互作用并促进微管聚合以确保有丝分裂进入。此外，CYR61与PLK1相互作用并在有丝分裂过程中积累，然后随着有丝分裂的结束而降解。CYR61的蛋白水解需要PLK1激酶活性，直接磷酸化CYR61上的两个保守基序，增强其与SCFE3复合物亚基FBW7的相互作用，并介导其通过蛋白酶体的降解。Ser167和Ser188磷酸化位点的突变大大增加了CYR61的稳定性,而CYR61的缺失延长了前期和中期，并延迟了后期的发作。总之,我们的发现强调了PLK1-FBW7通路对细胞内CYR61的精确控制，在有丝分裂过程中强调其作为微管相关蛋白的重要性。
