PBK/TOPK mediates Ikaros, Aiolos and CTCF displacement from mitotic chromosomes and alters chromatin accessibility at selected C2H2-zinc finger protein binding sites.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40987773.
- Also identified by DOI 10.1038/s41467-025-63740-4 and PMC identifier 12457614.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
PBK/TOPK is a mitotic kinase implicated in haematological and non-haematological cancers. Here we show that the key haemopoietic regulators Ikaros and Aiolos require PBK-mediated phosphorylation to dissociate from chromosomes in mitosis. Eviction of Ikaros is rapidly reversed by addition of the PBK-inhibitor OTS514, revealing dynamic regulation by kinase and phosphatase activities. To identify more PBK targets, we analysed loss of mitotic phosphorylation events in Pbk<sup>-/-</sup> preB cells and performed proteomic comparisons on isolated mitotic chromosomes. Among a large pool of C2H2-zinc finger targets, PBK is essential for evicting the CCCTC-binding protein CTCF and zinc finger proteins encoded by Ikzf1, Ikzf3, Znf131 and Zbtb11. PBK-deficient cells were able to divide but showed altered chromatin accessibility and nucleosome positioning consistent with CTCF retention. Our studies reveal that PBK controls the dissociation of selected factors from condensing mitotic chromosomes and contributes to their compaction.
Medical subject headings
- Ikaros Transcription Factor
- CCCTC-Binding Factor
- Mitosis
- Chromatin