A non-transcriptional mitotic function of POU/Oct factors ensures spindle assembly and chromosome segregation

The POU family, also known as Oct, of transcription factors (POU/Oct), are crucial regulators of cellular processes, including proliferation, cell fate determination, and cancer. Despite their importance, the specific molecular mechanisms by which they influence cell division remain largely unclear. Here, we show that Nub (also known as Pdm1), a Drosophila homolog of human POU2F1 (also known as Oct1), is essential for accurate mitotic progression in a non-transcriptional manner. Live imaging and immunostaining in Drosophila syncytial embryos reveal that its depletion leads to disorganized spindles, aberrant chromosome segregation and delayed mitotic progression. Similarly, reduction of POU2F1 in live human cells caused disorganized mitotic spindles and spindle collapse. Nub is enriched within the mitotic spindles, and this recruitment is independent of its sequence-specific DNA binding. Instead, it depends on the integrity of spindle microtubules and is regulated by mitosis-related motor proteins, and kinases. Our findings identify both fly Nub and human POU2F1 as important regulators of mitotic progression, acting to maintain spindle stability and proper elongation. The non-transcriptional mitotic role of Nub reveals a previously unrecognized mechanism of POU/Oct proteins and provides new insight into their potential oncogenic properties.