Phosphorylation of CBX8 by PKD1 suppresses PRC1 activity and promotes cell senescence.

Zhiqiang Fang, Doudou Liu, Yuanyuan Su, Fengxin Hao, Ruodong Qin, Guodong Li, Jun Chen

Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Integration of Chinese and Western Medicine, School of Basic Medical Science, Peking University, Beijing, 100191, China.Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Integration of Chinese and Western Medicine, School of Basic Medical Science, Peking University, Beijing, 100191, China. · pubmed

Paper

Abstract

The Polycomb group (PcG) protein chromobox 8 (CBX8) is the subunit of Polycomb repressive complex 1 (PRC1) and recognizes the trimethylation of histone H3 on Lysine 27 (H3K27me3), and coordinates with PRC2 complex to function as an epigenetic gene silencer. CBX8 plays a key role in cell proliferation, stem cell biology, cell senescence, and cancer development. However, the post-translational modifications of CBX8 remain poorly understood. Here, we report that protein kinase D1 (PKD1) interacts and phosphorylates CBX8 at Thr234 and Ser256 /311 residues. PKD1-mediated CBX8 phosphorylation at Thr234 reduced its expression level by promoting its ubiquitination-mediated degradation, whereas Ser256/311 phosphorylation decreased CBX8 binding to other PRC1 components BMI1 and RING1A. Overall, CBX8 phosphorylation by PKD1 impaired PRC1 complex integrity and activity, mitigated H2AK119ub1 level, caused the upregulation of multiple target genes repressed by CBX8, and decreased CBX8, H2AK119ub1, and H3K27me3 enrichment at INK4A/ARF locus, thereby derepressing p16

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Research summary

The paper claims that phosphorylation of CBX8 by PKD1 suppresses PRC1 activity, leading to increased cell senescence. This research is relevant as it explores the mechanisms of cell senescence, which is a key factor in aging and age-related diseases, potentially contributing to our understanding of the biological processes underlying longevity.

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