The tumor suppressor PTEN plays an important role in the regulation of cell survival, proliferation, and angiogenesis. Deregulated expression and/or activities of PTEN frequently result in tumor development. PTEN is a plasma-membrane lipid-phosphatase, functioning to antagonize the PI3K/AKT signaling pathway. It also has a role in the nucleus regulating mitotic progression and suppressing chromosomal instability during cell division. To date, the exact function of nuclear PTEN remains not entirely clear. Several recent studies have revealed that PTEN physically interacts with histones and regulates their post-translational modifications. We previously found that PTEN is heavily phosphorylated by Plk1, which regulates mototic progression and chromosomal instability through its physical interaction with mitotic checkpoint complex (MCC). Therefore, we asked whether PTEN directly interacted with epigenetic regulators and mediated histone modifications and whether PTEN-mediated histone modifications functioned as an important regulatory mechanism during the cell cycle. Here we demonstrated that PTEN was associated with Chromobox Homolog proteins (CBXs) which are part of PRC1 complex that mediates histone modifications. Among CBXs, CBX8 levels were high in mitosis, which were correlated with an increase in PTEN mono-ubiquitination, suggesting its potential involvement in mitotic progression. Supporting this notion, we showed that CBX8 was required for cell proliferation and mitotic progression. Moreover, CBX8 was associated with PTEN/MCC during mitosis and mediated histone H2AK119 mono-ubiquitination. Combined, these results strongly suggest that CBX8/PTEN/MCC plays a significant role in modifying histones and suppressing chromosomal instability during mitotic progression.

Citation Format: Byeong Hyeok Choi, Tania Marlyn Colon, Eunji Lee, Ziyue Kou, Wei Dai. PTEN plays a role in histone modifications during mitosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1969.