Golgi-localized Ring Finger Protein 121 is necessary for MYCN-driven neuroblastoma tumorigenesis.

ABSTRACT: MYCN amplification predicts poor prognosis in childhood neuroblastoma. To identify MYCN oncogenic signal dependencies we performed N-ethyl-N-nitrosourea (ENU) mutagenesis on the germline of neuroblastoma-prone TH-MYCN transgenic mice to generate founders which had lost tumorigenesis. Sequencing of the mutant mouse genomes identified the Ring Finger Protein 121 (RNF121^WT) gene mutated to RNF^M158R associated with heritable loss of tumorigenicity. While the RNF121^WT protein localised predominantly to the cis-Golgi Complex, the RNF121^M158R mutation in Helix 4 of its transmembrane domain caused reduced RNF121 protein stability and absent Golgi localisation. RNF121^WT expression markedly increased during TH-MYCN tumorigenesis, whereas hemizyg

SUBMITTER: Cheung BB 

PROVIDER: S-EPMC11473750 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature