生物
重编程
蛋白磷酸酶2
细胞生物学
细胞周期
基因
癌变
细胞周期蛋白依赖激酶
细胞生长
细胞周期检查点
E2F1
限制点
遗传学
磷酸化
磷酸酶
作者
Yuan Fu,Xiaofan Jia,Jinwei Yuan,Yuting Yang,Teng Zhang,Qiujing Yu,Jun Zhou,Ting Wang
标识
DOI:10.1016/j.devcel.2023.02.006
摘要
The cell cycle is key to life. After decades of research, it is unclear whether any parts of this process have yet to be identified. Fam72a is a poorly characterized gene and is evolutionarily conserved across multicellular organisms. Here, we have found that Fam72a is a cell-cycle-regulated gene that is transcriptionally and post-transcriptionally regulated by FoxM1 and APC/C, respectively. Functionally, Fam72a directly binds to tubulin and both the Aα and B56 subunits of PP2A-B56 to modulate tubulin and Mcl1 phosphorylation, which in turn affects the progression of the cell cycle and signaling of apoptosis. Moreover, Fam72a is involved in early responses to chemotherapy, and it efficiently antagonizes various anticancer compounds such as CDK and Bcl2 inhibitors. Thus, Fam72a switches the tumor-suppressive PP2A to be oncogenic by reprogramming its substrates. These findings identify a regulatory axis of PP2A and a protein member in the cell cycle and tumorigenesis regulatory network in human cells.
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