AKAP95 regulates ubiquitination and degradation of cyclin Ds/Es, influencing the G1/S transition of lung cancer cells

AKAP95调控细胞周期蛋白Ds/Es泛素化降解影响肺癌细胞G1/S转变

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作者:Zifeng Deng, Liangding Dou, Zhen Luo, Rong Liu, Jinwen Zhang, Jing Wang, Dai Wang, DongBei Guo, Ran An, Youliang Yao, Guihua Qiu, Yongxing Zhang

Abstract

A-kinase anchoring protein 95 (AKAP95) functions as a scaffold for protein kinase A. Prior work by our group has shown that AKAP95, in coordination with Connexin 43 (Cx43), modulates the expression of cyclin D and E proteins, thus affecting the cell cycle progression in lung cancer cells. In the current study, we confirmed that AKAP95 forms a complex with Cx43. Moreover, it associates with cyclins D1 and E1 during the G1 phase, leading to the formation of protein complexes that subsequently translocate to the nucleus. These findings indicate that AKAP95 might facilitate the nuclear transport of cyclins D1 and E1. Throughout this process, AKAP95 and Cx43 collectively regulate the expression of cyclin D, phosphorylate cyclin E1 proteins, and target their specific ubiquitin ligases, ultimately impacting cell cycle progression.

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