CBX2

Last update 08 May 2025

Basic Info

Synonyms

CBX2, CDCA6, chromobox 2

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Introduction

Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:21282530). PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:21282530). Binds to histone H3 trimethylated at 'Lys-9' (H3K9me3) or at 'Lys-27' (H3K27me3) (By similarity). Plays a role in the lineage differentiation of the germ layers in embryonic development (By similarity). Involved in sexual development, acting as activator of NR5A1 expression (PubMed:19361780).

100 Clinical Results associated with CBX2

100 Translational Medicine associated with CBX2

0 Patents (Medical) associated with CBX2

290

Literatures (Medical) associated with CBX2

14 Apr 2025·Oncogene

CBX2 as a therapeutic target in colorectal cancer: insights into the altered chromatin accessibility via RUNX1-CBX2-MAP4K1 axis

Article

Author: Tang, Chunming ; Gao, Wenqing ; Zhang, Shijie ; Wang, Bangting ; Wang, Jiankun ; Wu, Hao ; Liu, Li ; Guo, Yumeng ; Wang, Yan

Chromobox homolog 2 (CBX2), a component of the polycomb repressive complex 1, is overexpressed in various cancers, but its specific role in colorectal cancer (CRC) is not fully understood. This study aimed to characterize the functional and regulatory roles of CBX2 in CRC. Tissue microarray analysis revealed the elevated CBX2 levels in tumor compared to adjacent normal tissues, which is significantly correlated with poor prognosis. Gain and loss of function studies demonstrated that CBX2 significantly promoted CRC progression and chemoresistance in cell lines, patient-derived CRC organoids and xenografts. In the AOM/DSS mouse model, treatment with the innovatively-developed cy5-PBAE/siCBX2 nanoparticle significantly reduced tumor aggressiveness. Mechanistic studies unveiled that the transcription factor RUNX1 is the positive regulator of CBX2. RNA-seq, ATAC-seq and CUT & RUN results indicated CBX2 knockdown induced epigenetic changes, especially alterations in chromatin accessibility. Moreover, we further identified MAP4K1 as a target gene of RUNX1-CBX2, with significant clinical and prognostic relevance in CRC. Collectively, these findings suggest the pivotal role of RUNX1-CBX2-MAP4K1 axis in CRC progression and underscore CBX2 as a promising biomarker and therapeutic target. The regulatory function of CBX2 on chromatin accessibility and the role of the RUNX1-CBX2-MAP4K1-pERK axis in the progression of colorectal cancer.

04 Feb 2025·Proceedings of the National Academy of Sciences

CBX2 suppresses interferon signaling to diminish tumor immunogenicity via a noncanonical corepressor complex

Article

Author: Jiang, Wu ; Liu, Jinyun ; Bei, Jin-Xin ; Jin, Huan ; Li, Lin ; Zhang, Yiqun ; Cui, Lei ; Tan, Jing ; Xie, Chunyuan ; Liu, Yongxiang ; Zhao, Qi ; Zhang, Huanling ; Guo, Hui ; Wang, Zining ; Xia, Xiaojun ; Lin, Yanxun ; Wang, Xiaojuan ; Guo, Zixuan ; Chen, Yan-Xing ; He, Shuai ; Chen, Xu ; Wu, Jiaxin ; She, Yong ; Zhou, Penghui

Chromobox 2 (CBX2), a crucial component of the polycomb repressive complex (PRC), has been implicated in the development of various human cancers. However, its role in the regulation of tumor immunogenicity and immune evasion remains inadequately understood. In this study, we found that ablation of CBX2 led to tumor growth inhibition, activation of the tumor immune microenvironment, and enhanced therapeutic efficacy of anti-PD1 or adoptive T cell therapies by using murine syngeneic tumor models. By analysis of the CBX2-regulated transcriptional program coupled with mass spectrometry screening of CBX2-interacting proteins, we found that CBX2 suppresses interferon signaling independent of its function in the canonical PRC. Mechanistically, CBX2 directly interacts with RACK1 and facilitates the recruitment of HDAC1, which attenuates the H3K27ac modification on the promoter regions of interferon-stimulated genes, thereby suppressing interferon signaling. Consequently, CBX2 reduces tumor immunogenicity and enables immune evasion. Moreover, a high expression level of CBX2 is associated with immune suppressive tumor microenvironment and reduced efficacy of immunotherapy across various human cancer types. Our study identifies a noncanonical CBX2–RACK1–HDAC1 corepressor complex in suppression of tumor immunogenicity, thereby presenting a potential target and biomarker for tumor immunotherapy.

01 Feb 2025·Journal of Biological Chemistry

CBX2 promotes cervical cancer cell proliferation and resistance to DNA-damaging treatment via maintaining cancer stemness

Article

Author: Xu, Xiaohan ; Wang, Zanhong ; Sun, Si ; Du, Shi ; Wang, Xiaoman ; Yang, Lu ; Shen, Tiantian ; Shi, Ru ; Gao, Yumei ; Liu, Lin ; Wu, Qiulei ; Li, Wenhan ; Cai, Jing ; Liu, Xiaoli

Cervical cancer is the fourth most common malignancy and the fourth leading cause of cancer-related death among women. Advanced stages and resistance to treatment in cervical cancer induce cancer-related deaths. Although epigenetics has been known to play a vital role in tumor progression and resistance, the function of epigenetic regulators in cervical cancer is an area of investigation. In this study, we focused on an epigenetic regulator, polycomb repressor complex 1 in cervical cancer. Through bioinformatics analysis and immunochemistry, we subsequently identified chromobox 2CBX2), the deregulated subunit of polycomb repressor complex 1, which is upregulated in cervical cancer and associated with poor prognosis and unfavorable clinicopathological characteristics. We provided functional evidence demonstrating that CBX2 promoted cervical cancer cell proliferation. Furthermore, CBX2 exhibited an antiapoptotic effect, which induced resistance to cisplatin and ionizing radiation in cervical cancer cells. Moreover, CBX2 was involved in maintaining cancer stemness. These findings suggest that CBX2 plays an important role in cervical cancer progression and resistance to treatment, and may serve as a potential biomarker for prognosis and resistance as well as a potential therapeutic target.

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CBX2

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