Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; Institute of Biomedicine and FICANWest Cancer Center, University of Turku, Turku, Finland.
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; Institute of Biomedicine and FICANWest Cancer Center, University of Turku, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland.
Trends Cancer. 2024 Jan;10(1):52-64. doi: 10.1016/j.trecan.2023.09.001. Epub 2023 Oct 2.
Human cancers share requirements for phosphorylation-dependent signaling, mitotic hyperactivity, and survival after DNA damage. The oncoprotein CIP2A (cancerous inhibitor of PP2A) can coordinate all these cancer cell characteristics. In addition to controlling cancer cell phosphoproteomes via inhibition of protein phosphatase PP2A, CIP2A directly interacts with the DNA damage protein TopBP1 (topoisomerase II-binding protein 1). Consequently, CIP2A allows DNA-damaged cells to enter mitosis and is essential for mitotic cells that are defective in homologous recombination (HR)-mediated DNA repair (e.g., BRCA mutants). The CIP2A-TopBP1 complex is also important for clustering fragmented chromosomes at mitosis. Clinically, CIP2A is a disease driver for basal-like triple-negative breast cancer (BL-TNBC) and a promising cancer therapy target across many cancer types.
人类癌症都需要依赖磷酸化依赖的信号、有丝分裂活性增加以及 DNA 损伤后的存活。癌蛋白 CIP2A（蛋白磷酸酶 2A 的致癌抑制剂）可以协调所有这些癌细胞特征。除了通过抑制蛋白磷酸酶 2A 来控制癌细胞的磷酸化蛋白质组外，CIP2A 还直接与 DNA 损伤蛋白 TopBP1（拓扑异构酶 II 结合蛋白 1）相互作用。因此，CIP2A 允许受损 DNA 的细胞进入有丝分裂，并且对于同源重组（HR）介导的 DNA 修复有缺陷的有丝分裂细胞（例如 BRCA 突变体）是必需的。CIP2A-TopBP1 复合物对于有丝分裂时碎片化染色体的聚类也很重要。临床上，CIP2A 是基底样三阴性乳腺癌（BL-TNBC）的疾病驱动因子，也是许多癌症类型中很有前途的癌症治疗靶点。
