Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 52-64 |
| Number of pages | 13 |
| Journal | Trends in Cancer |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2024 |
| MoE publication type | A2 Review article in a scientific journal |
Funding
The original work by the authors cited in this article has been funded over the years by the Academy of Finland , Sigrid Juselius Foundation , Finnish Cancer Foundation , Jane and Aatos Erkko Foundation , University of Turku Graduate School , Breast Cancer Now , and the US Department of Defense , among other funding sources.
| Funders | Funder number |
|---|---|
| U.S. Department of Defense | |
| Academy of Finland | |
| Jane and Aatos Erkko Foundation | |
| Sigrid Jusélius Foundation | |
| Cancer Society of Finland | |
| Breast Cancer Now | |
| Turun yliopiston tutkijakoulu |
Keywords
- chromothripsis
- G2/M arrest
- PLK1
- RAD51
- TNBC