| 2000 |
CBX8 (HPC3) was identified as a novel Polycomb group protein that physically interacts with RING1 via its C-box domain; this interaction occurs in vivo preferentially with covalently modified forms of RING1. CBX8 co-localizes with other PcG proteins in PcG bodies and functions as a long-range transcriptional silencer when tethered to a reporter gene. |
Yeast two-hybrid screen, co-immunoprecipitation, fluorescence microscopy (co-localization), transcriptional reporter assay |
The Journal of biological chemistry |
Medium |
10825164
|
| 2007 |
CBX8, as a component of a PRC1 complex, directly binds the INK4A-ARF locus and represses it; ectopic CBX8 expression leads to Ink4a-Arf repression, bypass of senescence, and cellular immortalization in human and mouse diploid fibroblasts. |
Chromatin immunoprecipitation (ChIP), gene expression analysis, ectopic overexpression and loss-of-function in primary fibroblasts, genome-wide location analysis |
The EMBO journal |
High |
17332741
|
| 2011 |
CBX8 physically interacts with MLL-AF9 and TIP60, and is required for MLL-AF9-mediated transcriptional activation of HOX genes and leukemic transformation; point mutations disrupting the CBX8–MLL-AF9 interaction abolish HOX upregulation and leukemogenesis. |
Co-immunoprecipitation, point mutagenesis of MLL-AF9, Cbx8 knockout mice, leukemia transformation assays in vivo and in vitro |
Cancer cell |
High |
22094252
|
| 2013 |
CBX8 physically interacts with SIRT1 and cooperates with it to suppress p53 acetylation and p21WAF1 expression, thereby repressing premature senescence in breast cancer cells. CBX8 prevents SIRT1-inhibitor-induced senescence, and this effect is reversed by CBX8 knockdown. |
Co-immunoprecipitation, GST pull-down, fluorescence microscopy, transcriptional repression reporter, siRNA knockdown, Western blot |
Cancer letters |
Medium |
23474493
|
| 2014 |
A Cbx8-containing PRC1 complex facilitates transcriptional activation of developmental genes during ES cell differentiation; exchange of Cbx7 for Cbx8 in the PRC1 complex is required for effective activation of differentiation genes. Depletion of Cbx8 partially impairs activation of these genes. Activating Cbx8 associates with intact PRC1 components as shown by ChIP. |
ChIP-seq (genome-wide), gene expression microarray, interaction analysis (co-immunoprecipitation), siRNA depletion in mouse ES cells |
PLoS genetics |
Medium |
25500566
|
| 2016 |
EZH2 and BCL6 cooperate to assemble a non-canonical PRC1-BCOR-CBX8 complex at bivalent promoters in germinal center B cells; CBX8 binds H3K27me3 at these promoters and is required for stable complex association and for the resulting histone modifications, GC formation, and lymphomagenesis. |
Co-immunoprecipitation, ChIP, CBX8 inducible expression in GC B cells and lymphoma cells, mouse GC formation assays |
Cancer cell |
High |
27505670
|
| 2016 |
Cbx8 associates with non-PRC1 complexes containing WDR5, a component of H3K4 methyltransferase complexes, and together they maintain H3K4me3 levels on Notch-network gene promoters, positively regulating Notch signaling to promote mammary tumorigenesis. |
Loss-of-function screen, co-immunoprecipitation, ChIP-seq, Notch1 rescue experiment, in vivo tumorsphere assays |
Cell reports |
Medium |
27346354
|
| 2016 |
CBX8 rapidly accumulates at sites of DNA damage within 30 seconds in a PARP1-dependent (but ATM-independent) manner. CBX8 biochemically interacts with TRIM33, and its recruitment to DNA damage sites requires TRIM33. CBX8 knockdown reduces efficiency of both homologous and non-homologous recombination and increases cellular sensitivity to ionizing radiation. |
Live-cell imaging (laser microirradiation), co-immunoprecipitation, siRNA knockdown, DNA repair assays, ionizing radiation sensitivity assay |
The Journal of biological chemistry |
Medium |
27555324
|
| 2017 |
CBX8 activates AKT/β-catenin signaling in hepatocellular carcinoma via a non-canonical mechanism: it directly binds the EGR1 promoter to enhance its transcription and also interacts with EGR1 protein in the nucleus to prevent its degradation; additionally, CBX8 increases miR-365a-3p transcription, which promotes nuclear localization of β-catenin by targeting ZNRF1 3'-UTR. |
ChIP, co-immunoprecipitation, luciferase reporter assay, Western blot, ectopic expression and knockdown, in vivo tumor assays |
Cancer research |
Medium |
29066512
|
| 2017 |
CBX8 suppresses ESCC metastasis by directly binding the Snail promoter to repress Snail transcription, thereby inhibiting EMT. |
ChIP, luciferase reporter, siRNA knockdown, in vitro migration/invasion assays, in vivo metastasis assay |
Theranostics |
Medium |
28912889
|
| 2018 |
PIM1 kinase phosphorylates CBX8, promoting its proteasomal degradation, which leads to upregulation of p16 and induction of oncogene-induced senescence in human diploid fibroblasts. |
In vitro kinase assay, overexpression and knockdown of PIM1/CBX8, Western blot, senescence assays |
Biochemical and biophysical research communications |
Medium |
29763603
|
| 2019 |
The CBX8 chromodomain (CD) drives chromatin association through dual binding to H3K27me3 and DNA; structural characterization revealed integration of both activities and showed that the chromatin environment is critical for determining CBX8 CD function in chromatin association. |
In vitro binding assays, mutagenesis, structural characterization (NMR/biochemical), cellular chromatin association assays (ChIP), fluorescence polarization |
Nucleic acids research |
High |
30597065
|
| 2019 |
CBX8 chromodomain inhibitor SW2_110A (Kd ~800 nM) selectively displaces CBX8 from chromatin in cells in a chromodomain-dependent manner, reducing MLL-AF9 target gene expression (including HOXA9) and inhibiting THP1 leukemia cell proliferation, establishing the chromodomain as necessary for CBX8's role in MLL-AF9 transcriptional activation. |
DNA-encoded library selection, fluorescence polarization, cellular chromatin displacement assay, gene expression analysis, cell proliferation assay |
ACS chemical biology |
Medium |
31755685
|
| 2019 |
CBX8 upregulates LGR5 expression in a non-canonical manner by recruiting KMT2b (MLL4) to the LGR5 promoter, maintaining H3K4me3 to promote LGR5 transcription, thereby promoting cancer stemness; CBX8 mRNA stability is maintained by m6A methylation. |
ChIP-seq, RNA-seq, ChIP, co-immunoprecipitation, luciferase reporter assay, RNA immunoprecipitation, sphere formation assay |
Molecular cancer |
Medium |
31849331
|
| 2019 |
CBX8 interacts with YBX1; YBX1 knockdown impairs CBX8-mediated upregulation of CyclinD1 and cell proliferation in hepatocellular carcinoma cells, establishing a CBX8-YBX1-CyclinD1 axis in cell cycle regulation. |
Co-immunoprecipitation, bioinformatics, siRNA knockdown, Western blot, proliferation assays |
Aging |
Low |
31495785
|
| 2020 |
CBX8 binds the WNK2 promoter to suppress WNK2 expression, resulting in elevated MMP2 and RAC1 activity, thereby promoting invasion and migration in glioblastoma, breast cancer, and lung cancer cells. |
ChIP, luciferase reporter, ectopic expression and knockdown, invasion/migration assays in vitro and in vivo |
Molecular therapy oncolytics |
Medium |
33251331
|
| 2021 |
PIM1 phosphorylates CBX8 at serine 196, promoting its proteasomal degradation during erythroid differentiation of K562 CML cells; TRIM28 interacts with CBX8 and maintains its protein stability, and TRIM28 loss induces proteasomal degradation of CBX8 and accelerates erythroid differentiation. |
CRISPR-Cas9 screen, co-immunoprecipitation, proteomic analysis (mass spectrometry), siRNA knockdown, proteasome inhibitor treatment, Western blot, flow cytometry (CD235A) |
Molecules and cells |
Medium |
34253692
|
| 2021 |
KPNA2 promotes nuclear import of CBX8; CBX8 in turn downregulates PRDM1 by recruiting BCOR to the PRDM1 promoter region in bladder cancer cells. |
Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), nuclear fractionation, knockdown/overexpression, in vivo xenograft model |
Journal of translational medicine |
Medium |
33731128
|
| 2021 |
CBX8 acts as an RNA-binding protein that interacts with pre-miR-378a-3p via its RNA-binding domain and retains it in the nucleus, limiting nucleoplasmic transport and thereby inhibiting maturation of miR-378a-3p; mutation of the RNA-binding domain or nuclear localization signal of CBX8 abolishes this regulation. |
RNA immunoprecipitation, mutagenesis of RNA-binding domain and NLS, miRNA expression profiling, nucleocytoplasmic fractionation |
Human cell |
Medium |
33417156
|
| 2021 |
CBX8 positive allosteric modulator UNC7040 antagonizes H3K27me3 binding by CBX8 while increasing its interactions with nucleic acids, leading to eviction of CBX8-containing PRC1 from chromatin, loss of gene silencing, and reduced cancer cell proliferation. |
Quantitative cellular assay, in vitro biochemical binding assay, ChIP, gene expression analysis, cell proliferation assay |
Cell chemical biology |
Medium |
34715055
|
| 2022 |
CBX8 interacts with SET (an INHAT subunit) and together they co-bind the SUSD2 promoter to establish H2AK119ub1 and prevent histone H3 acetylation, resulting in transcriptional suppression of the tumor suppressor SUSD2 in ovarian carcinoma cells. |
FLAG affinity purification coupled with mass spectrometry, co-immunoprecipitation, ChIP, RNA-seq, functional rescue experiments |
Molecular cancer research : MCR |
Medium |
35894945
|
| 2023 |
CBX8 directly binds the promoters of CDKN2C and SCEL to establish H2AK119ub1, repressing their transcription and thereby promoting lung adenocarcinoma growth and metastasis; CBX8 depletion reduces H2AK119ub1 at these promoters and restores their expression. |
ChIP, RNA-seq, RT-PCR, knockdown and rescue experiments in cell culture and mouse models |
Journal of cellular physiology |
Medium |
37733753
|
| 2025 |
PKD1 (protein kinase D1) physically interacts with CBX8 and phosphorylates it at Thr234 and Ser256/311; phosphorylation at Thr234 promotes ubiquitination-mediated degradation of CBX8, while Ser256/311 phosphorylation decreases CBX8 binding to PRC1 components BMI1 and RING1A, impairing PRC1 complex integrity, reducing H2AK119ub1, and derepressing p16INK4A to facilitate cellular senescence. |
In vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, Western blot, ubiquitination assay, ChIP, gene expression analysis |
Oncogene |
High |
41398073
|
| 2025 |
PLK1 phosphorylates CBX8 at Ser265, driving GPX4 expression, which antagonizes BRAFi±EGFRi-induced ferroptosis in BRAFV600E colorectal cancer; disruption of this PLK1-CBX8-GPX4 axis by PLK1 inhibition enhances ferroptosis and overcomes drug resistance. |
Genome-wide CRISPR-Cas9 screen, in vitro kinase assay (PLK1), site mutagenesis, ChIP, Western blot, ferroptosis assays, organoid and PDX models |
Nature communications |
High |
40240371
|
| 2025 |
Cryo-electron tomography revealed that PRC1-CBX8-condensed chromatin forms a porous, accessible structure stabilized by multivalent dynamic interactions. Mechanistically, positively charged residues on the intrinsically disordered regions (IDRs) of CBX8 mask negative charges on DNA to stabilize condensed chromatin; PRC1 remains dynamic within condensates while the chromatin structure is static. In differentiated mouse ES cells, CBX8-bound chromatin remains accessible. |
Cryo-electron tomography (3D structural determination), in vitro chromatin condensation reconstitution, accessibility assays (ATAC-seq), mutagenesis |
Nature structural & molecular biology |
High |
39815045
|
| 2026 |
CBX8 inhibits autophagy-dependent senescence in colorectal cancer by transcriptionally repressing DDIT4 (a negative regulator of mTOR); CBX8 recruits TRIM28 to the DDIT4 promoter, maintaining H3K27me3 and repressing DDIT4 expression, thereby activating mTOR signaling. |
ChIP, co-immunoprecipitation, RNA-seq, CBX8 knockdown and overexpression in vitro and in vivo, mTOR signaling readouts, senescence assays |
International journal of biological sciences |
Medium |
41943835
|
| 2026 |
NSUN5 methylates CBX8 mRNA (m5C), stabilizing it and increasing CBX8 protein levels; elevated CBX8 then represses SOCS2 expression as part of PRC1, activating JAK-STAT3 signaling to promote gastric tumorigenesis. |
Catalytic mutant rescue (Nsun5C330A/C404A), RNA immunoprecipitation, Western blot, CBX8 inhibitor (SW2-110A) functional experiments, in vivo mouse tumor model |
Cellular signalling |
Medium |
42066830
|