Your browser doesn't support javascript.
loading
PD-L1 deglycosylation promotes its nuclear translocation and accelerates DNA double-strand-break repair in cancer.
Shu, Zhen; Dwivedi, Bhakti; Switchenko, Jeffrey M; Yu, David S; Deng, Xingming.
Afiliación
  • Shu Z; Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA, USA.
  • Dwivedi B; Bioinformatics and Systems Biology Shared Resource, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
  • Switchenko JM; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
  • Yu DS; Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA, USA.
  • Deng X; Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA, USA. xdeng4@emory.edu.
Nat Commun ; 15(1): 6830, 2024 Aug 09.
Article en En | MEDLINE | ID: mdl-39122729
ABSTRACT
Resistance to radiotherapy is a major barrier during cancer treatment. Here using genome-scale CRISPR/Cas9 screening, we identify CD274 gene, which encodes PD-L1, to confer lung cancer cell resistance to ionizing radiation (IR). Depletion of endogenous PD-L1 delays the repair of IR-induced DNA double-strand breaks (DSBs) and PD-L1 loss downregulates non-homologous end joining (NHEJ) while overexpression of PD-L1 upregulates NHEJ. IR induces translocation of PD-L1 from the membrane into nucleus dependent on deglycosylation of PD-L1 at N219 and CMTM6 and leads to PD-L1 recruitment to DSBs foci. PD-L1 interacts with Ku in the nucleus and enhances Ku binding to DSB DNA. The interaction between the IgC domain of PD-L1 and the core domain of Ku is required for PD-L1 to accelerate NHEJ-mediated DSB repair and produce radioresistance. Thus, PD-L1, in addition to its immune inhibitory activity, acts as mechanistic driver for NHEJ-mediated DSB repair in cancer.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleo Celular / Roturas del ADN de Doble Cadena / Antígeno B7-H1 / Reparación del ADN por Unión de Extremidades / Autoantígeno Ku Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleo Celular / Roturas del ADN de Doble Cadena / Antígeno B7-H1 / Reparación del ADN por Unión de Extremidades / Autoantígeno Ku Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido