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bioRxiv · 10.1101/2025.05.16.654605

BMI-1 Modulation and Trafficking During M Phase in Diffuse Intrinsic Pontine Glioma

Umaru, B.·Mishra, D.·Senthil Kumar, S.·Pang, H.-H.·Devine, B.·Khan, K.·Drissi, R.
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Abstract

BMI-1 (B cell-specific Moloney murine leukemia virus integration site 1) has been implicated in both normal and cancer cell biology. While the canonical function of BMI-1 involves epigenetic repression, novel extra-nuclear functions have been recently reported. In the present study, we demonstrate that the phosphorylation of BMI-1 in diffuse intrinsic pontine glioma (DIPG) cells occurs in M phase and that triggers simultaneous translocation of the phosphorylated BMI-1 to the cytoplasm. This translocation is mediated by the RanGTP-dependent transporter CRM1, also known as exportin. Furthermore, we uncovered a previously unidentified nuclear export signal (NES) in BMI-1 protein, suggesting an active transport type of modified BMI-1 mediated by CRM1. These findings associate BMI-1 phosphorylation with its trafficking in M phase. Collectively, this study sheds light on the molecular mechanisms underlying BMI-1 functions in DIPG, thereby potentially paving the way for the development of targeted therapeutic strategies related to M phase progression.

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Umaru, B., Mishra, D., Senthil Kumar, S., Pang, H.-H., Devine, B., Khan, K., Drissi, R.. 2025-05-22. BMI-1 Modulation and Trafficking During M Phase in Diffuse Intrinsic Pontine Glioma. https://doi.org/10.1101/2025.05.16.654605

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