人类癌症对磷酸化依赖性信号传导、有丝分裂过度活跃和 DNA 损伤后的存活都有共同的要求。癌蛋白 CIP2A（PP2A 的癌症抑制剂）可以协调所有这些癌细胞特征。除了通过抑制蛋白磷酸酶 PP2A 来控制癌细胞磷酸化蛋白质组外，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 DNA 损伤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）至关重要。 CIP2A-TopBP1 复合物对于有丝分裂时染色体片段的聚集也很重要。临床上，CIP2A 是基底样三阴性乳腺癌 (BL-TNBC) 的疾病驱动因素，也是多种癌症类型的有前景的癌症治疗靶点。版权所有 © 2023 作者。由爱思唯尔公司出版。保留所有权利。

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.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.