CIP2A coordinates phosphosignaling, mitosis, and the DNA damage response

被引：11

作者：

Nagelli, Srikar ^{[1
,2
,3
,4
]}

Westermarck, Jukka ^{[1
,2
,3
,4
,5
]}

机构：

[1] Univ Turku, Turku Biosci Ctr, Turku, Finland

[2] Abo Akad Univ, Turku, Finland

[3] Univ Turku, Inst Biomed, Turku, Finland

[4] Univ Turku, FICANWest Canc Ctr, Turku, Finland

[5] Univ Turku, InFLAMES Res Flagship Ctr, Turku, Finland

来源：

TRENDS IN CANCER | 2024年 / 10卷 / 01期

基金：

芬兰科学院;

关键词：

CANCEROUS INHIBITOR; PP2A; PROTEIN; EXPRESSION; KINASE; PHOSPHORYLATION; REPAIR; TUMORS; BRCA2; CELLS;

D O I：

10.1016/j.trecan.2023.09.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：52 / 64

页数：13

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