A Non-Transcriptional Mitotic Function of POU/Oct Factors Ensures Spindle Stability and Chromosome Segregation

POU/Oct transcription factors are critical 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/Pdm1, a Drosophila homolog of human POU2F1/Oct1, is essential for accurate mitotic progression in a non-transcriptional manner. Live imaging and immunostaining in Drosophila embryos reveal that its depletion leads to disorganized spindles, aberrant chromosome segregation and delayed mitotic progression. Similarly, reduction of POU2F1/Oct1 in live human cells caused disorganized mitotic spindles and spindle collapse. Nub/Pdm1 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/Pdm1 and human Oct1 as important regulators of mitotic progression, acting to maintain spindle stability and proper elongation. The non-transcriptional mitotic role of Nub/Pdm1 reveals a previously unrecognized mechanism of POU/Oct proteins and provides new insight into their potential oncogenic properties. Highlights - Nub/Pdm1 is vital for accurate mitotic progression in a non-transcriptional manner - Nub/Pdm1 preserves spindle integrity during rapid syncytial nuclear divisions - Nub/Pdm1 spindle enrichment depends on mitotic factors and intact microtubules - Nub and human Oct1 ensure proper chromosome segregation