Novel chromobox 2 inhibitory peptide decreases tumor progression.
Expert Opin Ther Targets
; 27(4-5): 361-371, 2023.
Article
em En
| MEDLINE
| ID: mdl-37243607
ABSTRACT
BACKGROUND:
The Polycomb Repressor Complex 1 (PRC1) is an epigenetic regulator of differentiation and development, consisting of multiple subunits including RING1, BMI1, and Chromobox. The composition of PRC1 dictates its function and aberrant expression of specific subunits contributes to several diseases including cancer. Specifically, the reader protein Chromobox2 (CBX2) recognizes the repressive modifications including histone H3 lysine 27 tri-methylation (H3K27me3) and H3 lysine 9 dimethylation (H3K9me2). CBX2 is overexpressed in several cancers compared to the non-transformed cell counterparts, it promotes both cancer progression and chemotherapy resistance. Thus, inhibiting the reader function of CBX2 is an attractive and unique anti-cancer approach. RESEARCH DESIGN &METHODS:
Compared with other CBX family members, CBX2 has a unique A/T-hook DNA binding domain that is juxtaposed to the chromodomain (CD). Using a computational approach, we constructed a homology model of CBX2 encompassing the CD and A/T hook domain. We used the model as a basis for peptide design and identified blocking peptides that are predicted to directly bind the CD and A/T-hook regions of CBX2. These peptides were tested in vitro and in vivo models.CONCLUSION:
The CBX2 blocking peptide significantly inhibited both 2D and 3D growth of ovarian cancer cells, downregulated a CBX2 target gene, and blunted tumor growth in vivo.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complexo Repressor Polycomb 1
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Expert Opin Ther Targets
Assunto da revista:
TERAPEUTICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos