CBX8 interacts with chromatin PTEN and is involved in regulating mitotic progression.

Byeong Hyeok Choi,Tania Marlyn Colon,Eunji Lee,Wei Dai,Ziyue Kou

doi:10.1111/cpr.13110

Byeong Hyeok Choi, Tania Marlyn Colon + Show 3 more

Open Access

https://doi.org/10.1111/cpr.13110

Copy DOI

Abstract

ObjectivesBesides its role in regulating phosphatidylinositol‐3 kinase (PI3K) signalling in the cytosol, PTEN also has a nuclear function. In this study, we attempted to understand the mechanism of chromatin PTEN in suppressing chromosomal instability during cell division.Materials and methodsImmunocoprecipitation, ectopic expression, and deletional analyses were used to identify the physical interaction between Chromobox Homolog protein 8 (CBX8) and PTEN, as well as the functional domain(s) of PTEN mediating the interaction. Cell synchronization followed by immunoblotting was employed to study cell cycle regulation of CBX8 and the functional interaction between chromatin PTEN and CBX8. Small interfering RNAs (siRNAs) were used to study the role of PTEN and CBX8 in modulating histone epigenetic markers during the cell cycle.ResultsPolycomb group (PcG) proteins including CBXs function to repress gene expression in a wide range of organisms including mammals. We recently showed that PTEN interacted with CBX8, a component of Polycomb Repressing Complex 1 (PRC1), and that CBX8 co‐localized with PTEN in the nucleus. CBX8 levels were high, coinciding with its phosphorylation in mitosis. Phosphorylation of CBX8 was associated with monoubiquitinated PTEN and phosphorylated‐BubR1 on chromatin. Moreover, CBX8 played an important role in cell proliferation and mitotic progression. Significantly, downregulation of either PTEN or CBX8 induced H3K27Me3 epigenetic marker in mitotic cells.ConclusionCBX8 is a new component that physically interacts with chromatin PTEN, playing an important role in regulating mitotic progression.

Highlights

We propose a model that depicts the physical interaction between Chromobox Homolog protein 8 (CBX8) and Phosphatase and tensin homolog is essential for cell proliferation.[48,49]
Great efforts have been made to understand the molecular basis by which nuclear Phosphatase and tensin homolog (PTEN) regulates gene expression, chromatin dynamics, and chromosomal stability.[51,54]
It is known that chromobox homolog proteins (CBXs) family proteins are integral components of Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2) and are required for targeting Polycomb Repressing Complex 1 (PRC1) to the chromatin.[11,19]

Summary

Introduction

We propose a model that depicts the physical interaction between CBX8 and Phosphatase and tensin homolog is essential for cell proliferation.[48,49] Our previous studies have shown that PTEN is required for proper mitotic timing and cell cycle progression by regulating MCC.[39,40,43] To determine whether CBX8, a PTEN-interacting protein, affected cell proliferation, we transfected cells with CBX8 siRNAs, or control siRNAs, and measured cell the proliferation rate.

Objectives

Results

Conclusion