CIP2A coordinates phosphosignaling, mitosis, and the DNA damage response

Srikar Nagelli, Jukka Westermarck*

*Corresponding author for this work

Research output: Contribution to journalReview Article or Literature Reviewpeer-review

1 Citation (Scopus)
5 Downloads (Pure)

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 languageEnglish
Pages (from-to)52-64
Number of pages13
JournalTrends in Cancer
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 2024
MoE publication typeA2 Review article in a scientific journal

Keywords

  • chromothripsis
  • G2/M arrest
  • PLK1
  • RAD51
  • TNBC

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