A forward genetic screen reveals novel independent regulators of ULBP1, an activating ligand for natural killer cells.
Elife
; 42015 Nov 13.
Article
em En
| MEDLINE
| ID: mdl-26565589
ABSTRACT
Recognition and elimination of tumor cells by the immune system is crucial for limiting tumor growth. Natural killer (NK) cells become activated when the receptor NKG2D is engaged by ligands that are frequently upregulated in primary tumors and on cancer cell lines. However, the molecular mechanisms driving NKG2D ligand expression on tumor cells are not well defined. Using a forward genetic screen in a tumor-derived human cell line, we identified several novel factors supporting expression of the NKG2D ligand ULBP1. Our results show stepwise contributions of independent pathways working at multiple stages of ULBP1 biogenesis. Deeper investigation of selected hits from the screen showed that the transcription factor ATF4 drives ULBP1 gene expression in cancer cell lines, while the RNA-binding protein RBM4 supports ULBP1 expression by suppressing a novel alternatively spliced isoform of ULBP1 mRNA. These findings offer insight into the stress pathways that alert the immune system to danger.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Ativação Linfocitária
/
Peptídeos e Proteínas de Sinalização Intracelular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Elife
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos