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bioRxiv · 10.1101/2024.04.26.591241

Loss of RNF2 delays tumour development in BAP1-deficient mesothelioma

Landman, N.·Hulsman, D.·Badhai, J.·van Lohuizen, M.
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Abstract

The tumour suppressor gene BAP1 is mutated in more than half of the malignant mesothelioma patients. This catalytic subunit of Polycomb repressive deubiquitinating (PR-DUB) complex, plays an important role in maintaining gene expression levels by deubiquitinating the PRC1-mediated histone H2A lysine 119 mono-ubiquitination (H2AK119ub1). Published studies report varying degrees of importance of H2AK119ub1 in Polycomb-regulated gene expression in different cell types. Recently published data by our own lab suggests a global redistribution of the H2AK119ub1 mark from promoter to intergenic regions upon loss of BAP1. PRC1-mediated mono-ubiquitination is dependent on the E3 ubiquitin ligase function of RNF2 (RING1B). Here, by knocking-out Rnf2, we show that loss of H2AK119ub1 levels leads to a decrease in clonogenic potential of Bap1-deficient mesothelioma cells in vitro and a delay in tumour onset in vivo.

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Landman, N., Hulsman, D., Badhai, J., van Lohuizen, M.. 2024-04-27. Loss of RNF2 delays tumour development in BAP1-deficient mesothelioma. https://doi.org/10.1101/2024.04.26.591241

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