Identification of Structural Elements of the Lysine Specific Demethylase 2B CxxC Domain Associated with Replicative Senescence Bypass in Primary Mouse Cells.
Protein J
; 39(3): 232-239, 2020 06.
Article
en En
| MEDLINE
| ID: mdl-32270414
ABSTRACT
BACKGROUND:
Lysine specific demethylase 2B, KDM2B, regulates genes that participate in cellular development, morphogenesis, differentiation and metabolism as a component of the polycomb repressive complex 1 (PRC1). The CxxC finger of KDM2B is responsible for the DNA binding capacity of this epigenetic regulator, acting as a sampling mechanism across chromatin for gene repressionOBJECTIVES:
The molecular determinants of the CxxC-DNA interaction remain largely unknown, revealing a significant knowledge gap to be explored. Our goal was to elucidate the key residues of the CxxC domain that contribute to its function as well as to further elaborate on the significance of this domain in the KDM2B roleMETHODS:
By using electrophoresis mobility swift assay, we identified structural elements of CxxC domain that participate in the DNA recognition. We created mouse embryonic fibroblasts overexpressing different truncated and point-mutated mouse KDM2B variants to examine the contribution of the KDM2B domains in replicative senescence bypassRESULTS:
In this study, we show that only the CxxC finger is essential for the ability of mKDM2B to bypass replicative senescence in primary cells by ink4A-Arf-ink4B locus repression, and that this is mediated by specific interactions of residues R585, K608 and K616 with non-methylated CpG containing DNACONCLUSIONS:
These results provide new structural insights into the molecular interactions of CxxC and could serve as a stepping-stone for developing domain-specific inhibitors for KDM2B.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN
/
Senescencia Celular
/
Inhibidor p16 de la Quinasa Dependiente de Ciclina
/
Factor 1 de Ribosilacion-ADP
/
Proteínas F-Box
/
Inhibidor p15 de las Quinasas Dependientes de la Ciclina
/
Histona Demetilasas con Dominio de Jumonji
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Protein J
Asunto de la revista:
BIOQUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Grecia